SEARCH

Search Details

ITO Toshiki
Biosignal Research Center
Professor

Researcher basic information

■ Research news
■ Research Areas
  • Life sciences / Functional biochemistry
■ Committee History
  • 2015 - Present, 日本細胞生物学会, 代議員
  • 2015 - Present, 日本生化学会, 評議員
  • 2013 - Present, 日本脂質生化学会, 幹事

Research activity information

■ Award
  • Oct. 2009 社団法人日本生化学会, 日本生化学会奨励賞, エンドサイトーシスにおける細胞膜の形状制御機構
    Itoh Toshiki

■ Paper
  • Linting Kou, Yumeng Wan, Yuri L. Nemoto, Kazuya Tsujita, Toshiki Itoh
    Elsevier BV, Jun. 2025, Biochemical and Biophysical Research Communications, 766, 151846 - 151846
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yumeng Wan, Yuri L. Nemoto, Tsukasa Oikawa, Kazunori Takano, Takahiro K. Fujiwara, Kazuya Tsujita, Toshiki Itoh
    Osteoclasts are multinucleated giant cells that are formed by the fusion of precursor cells. Cell–cell fusion is mediated by membrane protrusion driven by actin reorganization, but the role of membrane mechanics in this process is unknown. Utilizing live-cell imaging, optical tweezers, manipulation of membrane-to-cortex attachment (MCA), and genetic interference, we show that a decrease in plasma membrane (PM) tension is a mechanical prerequisite for osteoclast fusion. Upon RANKL-induced differentiation, ezrin expression in fusion progenitor cells is reduced, resulting in a decrease in MCA-dependent PM tension. A forced elevation of PM tension by reinforcing the MCA conversely suppresses cell–cell fusion. Mechanistically, reduced PM tension leads to membrane protrusive invadosome formation driven by membrane curvature-inducing/sensing BAR proteins, thereby promoting cell–cell fusion. These findings provide insights into the mechanism of cell–cell fusion under the control of membrane mechanics.
    Rockefeller University Press, May 2025, Journal of Cell Biology, 224(7) (7)
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Toshiki Itoh, Kazuya Tsujita
    Elsevier BV, Apr. 2023, Current Opinion in Cell Biology, 81, 102173 - 102173
    [Refereed][Invited]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Kaori Kanemaru, Makoto Shimozawa, Manabu Kitamata, Rikuto Furuishi, Hinako Kayano, Yui Sukawa, Yuuki Chiba, Takatsugu Fukuyama, Junya Hasegawa, Hiroki Nakanishi, Takuma Kishimoto, Kazuya Tsujita, Kazuma Tanaka, Toshiki Itoh, Junko Sasaki, Takehiko Sasaki, Kiyoko Fukami, Yoshikazu Nakamura
    Abstract Epithelial cells provide cell-cell adhesion that is essential to maintain the integrity of multicellular organisms. Epithelial cell-characterizing proteins, such as epithelial junctional proteins and transcription factors are well defined. However, the role of lipids in epithelial characterization remains poorly understood. Here we show that the phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] is enriched in the plasma membrane (PM) of epithelial cells. Epithelial cells lose their characteristics upon depletion of PM PI(4,5)P2, and synthesis of PI(4,5)P2 in the PM results in the development of epithelial-like morphology in osteosarcoma cells. PM localization of PARD3 is impaired by depletion of PM PI(4,5)P2 in epithelial cells, whereas expression of the PM-targeting exocyst-docking region of PARD3 induces osteosarcoma cells to show epithelial-like morphological changes, suggesting that PI(4,5)P2 regulates epithelial characteristics by recruiting PARD3 to the PM. These results indicate that a high level of PM PI(4,5)P2 plays a crucial role in the maintenance of epithelial characteristics.
    Springer Science and Business Media LLC, Dec. 2022, Nature Communications, 13(1) (1)
    [Refereed]
    Scientific journal

  • Shinya Yuge, Koichi Nishiyama, Yuichiro Arima, Yasuyuki Hanada, Eri Oguri-Nakamura, Sanshiro Hanada, Tomohiro Ishii, Yuki Wakayama, Urara Hasegawa, Kazuya Tsujita, Ryuji Yokokawa, Takashi Miura, Toshiki Itoh, Kenichi Tsujita, Naoki Mochizuki, Shigetomo Fukuhara
    Abstract Angiogenesis is regulated in coordinated fashion by chemical and mechanical cues acting on endothelial cells (ECs). However, the mechanobiological mechanisms of angiogenesis remain unknown. Herein, we demonstrate a crucial role of blood flow-driven intraluminal pressure (IP) in regulating wound angiogenesis. During wound angiogenesis, blood flow-driven IP loading inhibits elongation of injured blood vessels located at sites upstream from blood flow, while downstream injured vessels actively elongate. In downstream injured vessels, F-BAR proteins, TOCA1 and CIP4, localize at leading edge of ECs to promote N-WASP-dependent Arp2/3 complex-mediated actin polymerization and front-rear polarization for vessel elongation. In contrast, IP loading expands upstream injured vessels and stretches ECs, preventing leading edge localization of TOCA1 and CIP4 to inhibit directed EC migration and vessel elongation. These data indicate that the TOCA family of F-BAR proteins are key actin regulatory proteins required for directed EC migration and sense mechanical cell stretching to regulate wound angiogenesis.
    Springer Science and Business Media LLC, Dec. 2022, Nature Communications, 13(1) (1)
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Reiko Satow, Shinobu Asada, Yoshikazu Nakamura, Luis Arnes, Keisuke Sako, Yasuyuki Fujita, Kiyoko Fukami, Toshiki Itoh
    Abstract Malignancy is associated with changes in cell mechanics that contribute to extensive cell deformation required for metastatic dissemination. We hypothesized that the cell-intrinsic physical factors that maintain epithelial cell mechanics could function as tumor suppressors. Here we show, using optical tweezers, genetic interference, mechanical perturbations, and in vivo studies, that epithelial cells maintain higher plasma membrane (PM) tension than their metastatic counterparts and that high PM tension potently inhibits cancer cell migration and invasion by counteracting membrane curvature sensing/generating BAR family proteins. This tensional homeostasis is achieved by membrane-to-cortex attachment (MCA) regulated by ERM proteins, whose disruption spontaneously transforms epithelial cells into a mesenchymal migratory phenotype powered by BAR proteins. Consistently, the forced expression of epithelial–mesenchymal transition (EMT)-inducing transcription factors results in decreased PM tension. In metastatic cells, increasing PM tension by manipulating MCA is sufficient to suppress both mesenchymal and amoeboid 3D migration, tumor invasion, and metastasis by compromising membrane-mediated mechanosignaling by BAR proteins, thereby uncovering a previously undescribed mechanical tumor suppressor mechanism.
    Springer Science and Business Media LLC, Oct. 2021, Nature Communications, 12(1) (1)
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tomoko Kamasaki, Yumi Miyazaki, Susumu Ishikawa, Kazuya Hoshiba, Keisuke Kuromiya, Nobuyuki Tanimura, Yusuke Mori, Motosuke Tsutsumi, Tomomi Nemoto, Ryota Uehara, Shiro Suetsugu, Toshiki Itoh, Yasuyuki Fujita
    At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic analysis that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a positive role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing "protrusion to protrusion response" between normal and RasV12-transformed cells.
    Sep. 2021, iScience, 24(9) (9), 102994 - 102994, English, International magazine
    [Refereed]
    Scientific journal

  • Toshinori Motegi, Kingo Takiguchi, Yohko Tanaka-Takiguchi, Toshiki Itoh, Ryugo Tero
    We characterized the size, distribution, and fluidity of microdomains in a lipid bilayer containing phosphatidylinositol (PI) and revealed their roles during the two-dimensional assembly of a membrane deformation protein (FBP17). The morphology of the supported lipid bilayer (SLB) consisting of PI and phosphatidylcholine (PC) on a mica substrate was observed with atomic force microscope (AFM). Single particle tracking (SPT) was performed for the PI+PC-SLB on the mica substrate by using the diagonal illumination setup. The AFM topography showed that PI-derived submicron domains existed in the PI+PC-SLB. The spatiotemporal dependence of the lateral lipid diffusion obtained by SPT showed that the microdomain had lower fluidity than the surrounding region and worked as the obstacles for the lipid diffusion. We observed the two-dimensional assembly of FBP17, which is one of F-BAR family proteins included in endocytosis processes and has the function generating lipid bilayer tubules in vitro. At the initial stage of the FBP17 assembly, the PI-derived microdomain worked as a scaffold for the FBP17 adsorption, and the fluid surrounding region supplied FBP17 to grow the FBP17 domain via the lateral molecular diffusion. This study demonstrated an example clearly revealing the roles of two lipid microregions during the protein reaction on a lipid bilayer.
    May 2021, Membranes, 11(5) (5), 339, English, International magazine
    [Refereed]
    Scientific journal

  • Lu Yan, Kazuya Tsujita, Yasuyuki Fujita, Toshiki Itoh
    Corresponding, Wiley, May 2021, FEBS Letters, 595(9) (9), 1303 - 1312
    [Refereed]
    Scientific journal

  • Imen Jebri, Kazuya Tsujita, Yasuyuki Fujita, Toshiki Itoh
    Corresponding, Elsevier BV, Mar. 2021, Biochemical and Biophysical Research Communications, 543, 15 - 22
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Junya Hasegawa, Imen Jebri, Hikaru Yamamoto, Kazuya Tsujita, Emi Tokuda, Hideki Shibata, Masatoshi Maki, Toshiki Itoh
    Ubiquitinated membrane proteins such as epidermal growth factor receptor (EGFR) are delivered to early endosomes and then sorted to lysosomes via multivesicular bodies (MVBs) for degradation. The regulatory mechanism underlying formation of intralumenal vesicles en route to generation of MVBs is not fully understood. In this study, we found that SH3YL1, a phosphoinositide-binding protein, had a vesicular localization pattern overlapping with internalized EGF in endosomes in the degradative pathway. Deficiency of SH3YL1 prevents EGF trafficking from early to late endosomes and inhibits degradation of EGFR. Moreover, we show that SH3YL1 mediates EGFR sorting into MVBs in a manner dependent on its carboxy-terminal SH3 domain, which is necessary for the interaction with an ESCRT-I component, Vps37B. Taken together, our observations reveal an indispensable role of SH3YL1 in MVB-sorting and EGFR degradation mediated by ESCRT complexes.
    Corresponding, The Company of Biologists, Oct. 2019, Journal of Cell Science
    [Refereed]
    Scientific journal

  • Toshihiro Masuda, Kentarou Baba, Takeshi Nomura, Kazuya Tsujita, Tomo Murayama, Toshiki Itoh, Tomoka Takatani-Nakase, Masahiro Sokabe, Naoyuki Inagaki, Shiroh Futaki
    Abstract Tension in cell membranes is closely related to various cellular events, including cell movement and morphogenesis. Therefore, modulation of membrane tension can be a new approach for manipulating cellular events. Here, we show that an amphipathic peptide derived from the influenza M2 protein (M2[45–62]) yields lamellipodia at multiple sites in the cell. Effect of M2[45–62] on cell membrane tension was evaluated by optical tweezer. The membrane tension sensor protein FBP17 was involved in M2[45–62]-driven lamellipodium formation. Lysine-to-arginine substitution in M2[45–62] further enhanced its activity of lamellipodium formation. M2[45–62] had an ability to reduce cell motility, evaluated by scratch wound migration and transwell migration assays. An increase in neurite outgrowth was also observed after treatment with M2[45–62]. The above results suggest the potential of M2[45–62] to modulate cell movement and morphology by modulating cell membrane tension.
    Springer Science and Business Media LLC, Jun. 2019, Communications Biology, 2(1) (1)
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Hikaru Yamamoto, Akihiro Kondo, Toshiki Itoh
    Corresponding, Elsevier BV, Jan. 2018, Biochemical and Biophysical Research Communications, 495(1) (1), 1522 - 1527
    [Refereed]
    Scientific journal

  • Hideaki Ando, Matsumi Hirose, Laura Gainche, Katsuhiro Kawaai, Benjamin Bonneau, Takeshi Ijuin, Toshiki Itoh, Tadaomi Takenawa, Katsuhiko Mikoshiba
    Oct. 2015, PLOS ONE, 10(10) (10), e0141569 - e0141569
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Tadaomi Takenawa, Toshiki Itoh
    Corresponding, Jun. 2015, Nature Cell Biology, 17(6) (6), 749 - 758
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Toshiki Itoh
    Corresponding, Jun. 2015, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1851(6) (6), 824 - 831
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Emi Tokuda, Toshiki Itoh, Junya Hasegawa, Takeshi Ijuin, Yukiko Takeuchi, Yasuhiro Irino, Miki Fukumoto, Tadaomi Takenawa
    Jun. 2014, Cancer Research, 74(11) (11), 3054 - 3066
    [Refereed]
    Scientific journal

  • Cuifang Li, Ayako Kita, Yuuka Hashimoto, Misako Ihara, Ayaka Kato, Naoya Ogura, Akira Doi, Masahide Oku, Toshiki Itoh, Yasuyoshi Sakai, Reiko Sugiura
    Mar. 2014, Genes to Cells, 19(3) (3), 177 - 197
    [Refereed]
    Scientific journal

  • Daisuke Yamazaki, Toshiki Itoh, Hiroaki Miki, Tadaomi Takenawa
    American Society for Cell Biology (ASCB), Nov. 2013, Molecular Biology of the Cell, 24(21) (21), 3393 - 3405
    [Refereed]
    Scientific journal

  • Yohko Tanaka-Takiguchi, Toshiki Itoh, Kazuya Tsujita, Shunsuke Yamada, Miho Yanagisawa, Kei Fujiwara, Akihisa Yamamoto, Masatoshi Ichikawa, Kingo Takiguchi
    Jan. 2013, Langmuir, 29(1) (1), 328 - 336
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Akihiro Kondo, Shusaku Kurisu, Junya Hasegawa, Toshiki Itoh, Tadaomi Takenawa
    Corresponding, Jan. 2013, Journal of Cell Science
    [Refereed]
    Scientific journal

  • T. Itoh, J. Hasegawa
    Corresponding, Jan. 2013, Journal of Biochemistry, 153(1) (1), 21 - 29
    [Refereed]
    Scientific journal

  • Hyeon-Cheol Lee, Takao Inoue, Junko Sasaki, Takuya Kubo, Shinji Matsuda, Yasuko Nakasaki, Mitsuharu Hattori, Fumiharu Tanaka, Osamu Udagawa, Nozomu Kono, Toshiki Itoh, Hideo Ogiso, Ryo Taguchi, Makoto Arita, Takehiko Sasaki, Hiroyuki Arai
    Dec. 2012, Molecular Biology of the Cell, 23(24) (24), 4689 - 4700
    [Refereed]
    Scientific journal

  • Katsuhiro Kato, Tsubasa Yazawa, Kentaro Taki, Kazutaka Mori, Shujie Wang, Tomoki Nishioka, Tomonari Hamaguchi, Toshiki Itoh, Tadaomi Takenawa, Chikako Kataoka, Yoshiharu Matsuura, Mutsuki Amano, Toyoaki Murohara, Kozo Kaibuchi
    Jul. 2012, Molecular Biology of the Cell, 23(13) (13), 2593 - 2604
    [Refereed]
    Scientific journal

  • Junya Hasegawa, Kazuya Tsujita, Tadaomi Takenawa, Toshiki Itoh
    Corresponding, Jul. 2012, Molecular Biology of the Cell, 23(13) (13), 2481 - 2489
    [Refereed]
    Scientific journal

  • Yasuhiro Irino, Emi Tokuda, Junya Hasegawa, Toshiki Itoh, Tadaomi Takenawa
    Apr. 2012, Journal of Lipid Research, 53(4) (4), 810 - 819
    [Refereed]
    Scientific journal

  • [Mechanisms for the regulation of the plasma membrane curvature in endocytosis].
    Toshiki Itoh
    Jan. 2012, Seikagaku. The Journal of Japanese Biochemical Society, 84(1) (1), 5 - 17, Japanese, Domestic magazine
    [Refereed][Invited]
    Scientific journal

  • F. Wang, T. Ijuin, T. Itoh, T. Takenawa
    Jul. 2011, Journal of Biochemistry, 150(1) (1), 83 - 93
    [Refereed]
    Scientific journal

  • Junya Hasegawa, Emi Tokuda, Takeshi Tenno, Kazuya Tsujita, Haruko Sawai, Hidekazu Hiroaki, Tadaomi Takenawa, Toshiki Itoh
    Reversible interactions between cytosolic proteins and membrane lipids such as phosphoinositides play important roles in membrane morphogenesis driven by actin polymerization. In this paper, we identify a novel lipid-binding module, which we call the SYLF domain (after the SH3YL1, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins that contain it), that is highly conserved from bacteria to mammals. SH3YL1 (SH3 domain containing Ysc84-like 1) strongly bound to phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3) and several D5-phosphorylated phosphoinositides through its SYLF domain and was localized to circular dorsal ruffles induced by platelet-derived growth factor stimulation. Interestingly, SHIP2 (the PI(3,4,5)P3 5-phosphatase, src-homology 2–containing inositol-5-phosphatase 2) was identified as a binding partner of SH3YL1, and knockdown of these proteins significantly suppressed dorsal ruffle formation. Phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2), which is mainly synthesized from PI(3,4,5)P3 by the action of SHIP2, was enriched in dorsal ruffles, and PI(3,4)P2 synthesis strongly correlated with formation of the circular membrane structure. These results provide new insight into the molecular mechanism of dorsal ruffle formation and its regulation by phosphoinositide metabolism.
    Corresponding, Rockefeller University Press, May 2011, Journal of Cell Biology, 193(5) (5), 901 - 916
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Toshiki Itoh, Akihiro Kondo, Masaaki Oyama, Hiroko Kozuka-Hata, Yasuhiro Irino, Junya Hasegawa, Tadaomi Takenawa
    Feb. 2010, Journal of Biological Chemistry, 285(9) (9), 6781 - 6789
    [Refereed]
    Scientific journal

  • Mikito Takefuji, Hiroyuki Asano, Kazutaka Mori, Mutsuki Amano, Katsuhiro Kato, Takashi Watanabe, Yasuhiro Morita, Akira Katsumi, Toshiki Itoh, Tadaomi Takenawa, Akihiro Hirashiki, Hideo Izawa, Kozo Nagata, Haruo Hirayama, Fumimaro Takatsu, Tomoki Naoe, Mitsuhiro Yokota, Kozo Kaibuchi
    Jan. 2010, Journal of Human Genetics, 55(1) (1), 42 - 49
    [Refereed]
    Scientific journal

  • Hiroshi Yamada, Sergi Padilla-Parra, Sun-Joo Park, Toshiki Itoh, Mathilde Chaineau, Ilaria Monaldi, Ottavio Cremona, Fabio Benfenati, Pietro De Camilli, Maïté Coppey-Moisan, Marc Tramier, Thierry Galli, Kohji Takei
    Dec. 2009, Journal of Biological Chemistry, 284(49) (49), 34244 - 34256
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Junya Hasegawa, Kazuya Tsujita, Yasunori Kanaho, Tadaomi Takenawa
    American Association for the Advancement of Science (AAAS), Sep. 2009, Science Signaling, 2(87) (87)
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Tadaomi Takenawa
    Lead, Sep. 2009, Progress in Lipid Research, 48(5) (5), 298 - 305
    [Refereed]
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Tsukasa Oikawa, Toshiki Itoh, Tadaomi Takenawa
    Jul. 2008, Journal of Cell Biology, 182(1) (1), 157 - 169
    [Refereed]
    Scientific journal

  • Emi Tokuda, Naoya Fujita, Tomoko Oh-hara, Shigeo Sato, Atsuo Kurata, Ryohei Katayama, Toshiki Itoh, Tadaomi Takenawa, Kohei Miyazono, Takashi Tsuruo
    Abstract The serine/threonine kinase Akt plays a central role in cell survival and proliferation. Its activation is linked to tumorigenesis in several human cancers. Although many Akt substrates have been elucidated, the Akt-binding proteins that regulate Akt function remain unclear. We report herein having identified casein kinase 2–interacting protein-1 (CKIP-1) as an Akt pleckstrin homology (PH) domain-binding protein with Akt inhibitory function. CKIP-1 formed a complex with each Akt isoform (Akt1, Akt2, and Akt3) via its NH2 terminus. Dimerization of CKIP-1 via its leucine zipper (LZ) motif at the COOH terminus was found to be associated with Akt inactivation because deletion of the LZ motif eliminated Akt inhibitory function, although it could still bind to Akt. Expression of the NH2 terminus–deleted CKIP-1 mutant containing the LZ motif, but lacking Akt-binding ability, induced Akt phosphorylation and activation by sequestering the ability of endogenous CKIP-1 to bind to Akt. Stable CKIP-1 expression caused Akt inactivation and cell growth inhibition in vitro. In addition, the growth of stable CKIP-1 transfectants xenografted into nude mice was slower than that of mock transfectants. These results indicate that CKIP-1, a novel Akt PH domain-interacting protein, would be a candidate of tumor suppressor with an Akt inhibitory function. [Cancer Res 2007;67(20):9666–76]
    American Association for Cancer Research (AACR), Oct. 2007, Cancer Research, 67(20) (20), 9666 - 9676
    [Refereed]
    Scientific journal

  • Masahiro Furutani, Kazuya Tsujita, Toshiki Itoh, Takeshi Ijuin, Tadaomi Takenawa
    Aug. 2006, Analytical Biochemistry, 355(1) (1), 8 - 18
    [Refereed]
    Scientific journal

  • T ITOH, P DECAMILLI
    Elsevier BV, Aug. 2006, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1761(8) (8), 897 - 912
    [Refereed]
    Scientific journal

  • Tadaomi Takenawa, Toshiki Itoh
    May 2006, IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), 58(5-6) (5-6), 296 - 303
    [Refereed]
    Scientific journal

  • Masahiro Furutani, Toshiki Itoh, Takeshi Ijuin, Kazuya Tsujita, Tadaomi Takenawa
    Apr. 2006, The Journal of Biochemistry, 139(4) (4), 663 - 670
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Kai S. Erdmann, Aurelien Roux, Bianca Habermann, Hauke Werner, Pietro De Camilli
    Dec. 2005, Developmental Cell, 9(6) (6), 791 - 804
    [Refereed]
    Scientific journal

  • Tsukasa Oikawa, Hideki Yamaguchi, Toshiki Itoh, Masayoshi Kato, Takeshi Ijuin, Daisuke Yamazaki, Shiro Suetsugu, Tadaomi Takenawa
    May 2004, Nature Cell Biology, 6(5) (5), 420 - 426
    Scientific journal

  • Toshiki Itoh, Pietro De Camilli
    May 2004, Nature, 429(6988) (6988), 141 - 143
    [Refereed]
    Scientific journal

  • Kazuya Tsujita, Toshiki Itoh, Takeshi Ijuin, Akitsugu Yamamoto, Assia Shisheva, Jocelyn Laporte, Tadaomi Takenawa
    Apr. 2004, Journal of Biological Chemistry, 279(14) (14), 13817 - 13824
    [Refereed]
    Scientific journal

  • Regulation of endocytosis by phosphatidylinositol 4,5-bisphosphate and ENTH proteins.
    T Itoh, T Takenawa
    Clathrin-mediated endocytosis starts by a recruitment of endocytic proteins to the plasma membrane to induce invagination of lipid bilayer and subsequent vesicule formation. The recruitment of these components requires PtdIns(4,5)P2, a phosphoinositide on the plasma membrane. Although it is well known that the synthesis as well as the disruption of this lipid is important, recent studies have revealed the indispensable roles of direct interaction between PtdIns(4,5)P2 and the endocytic machinery. The ENTH domain is a newly found PtdIns(4,5)P2 binding unit conserved among endocytic proteins like epsins, AP180, and the Hip1/Sla2 family. This review focuses on the essential roles of PtdIns(4,5)P2 and its specific binding partner, the ENTH domain, in clathrin-mediated endocytosis.
    2004, Current topics in microbiology and immunology, 282, 31 - 47, English, International magazine
    [Refereed][Invited]
    Scientific journal

  • Makiko Otsuki, Toshiki Itoh, Tadaomi Takenawa
    Feb. 2003, Journal of Biological Chemistry, 278(8) (8), 6461 - 6469
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Tadaomi Takenawa
    Sep. 2002, Cellular Signalling, 14(9) (9), 733 - 743
    [Refereed]
    Scientific journal

  • Tadaomi Takenawa, Toshiki Itoh
    Elsevier BV, Oct. 2001, Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1533(3) (3), 190 - 206
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Seizo Koshiba, Takanori Kigawa, Akira Kikuchi, Shigeyuki Yokoyama, Tadaomi Takenawa
    Endocytic proteins such as epsin, AP180, and Hip1R (Sla2p) share a conserved modular region termed the epsin NH 2 -terminal homology (ENTH) domain, which plays a crucial role in clathrin-mediated endocytosis through an unknown target. Here, we demonstrate a strong affinity of the ENTH domain for phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]. With nuclear magnetic resonance analysis of the epsin ENTH domain, we determined that a cleft formed with positively charged residues contributed to phosphoinositide binding. Overexpression of a mutant, epsin Lys 76 → Ala 76 , with an ENTH domain defective in phosphoinositide binding, blocked epidermal growth factor internalization in COS-7 cells. Thus, interaction between the ENTH domain and PtdIns(4,5)P 2 is essential for endocytosis mediated by clathrin-coated pits.
    Lead, American Association for the Advancement of Science (AAAS), Feb. 2001, Science, 291(5506) (5506), 1047 - 1051
    [Refereed]
    Scientific journal

  • Sun Joo Park, Toshiki Itoh, Tadaomi Takenawa
    Elsevier BV, Feb. 2001, Journal of Biological Chemistry, 276(7) (7), 4781 - 4787
    [Refereed]
    Scientific journal

  • Yingjie Zhang, Reiko Sugiura, Yabin Lu, Masako Asami, Takuya Maeda, Toshiki Itoh, Tadaomi Takenawa, Hisato Shuntoh, Takayoshi Kuno
    Elsevier BV, Nov. 2000, Journal of Biological Chemistry, 275(45) (45), 35600 - 35606
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Hisamitsu Ishihara, Yoshikazu Shibasaki, Yoshitomo Oka, Tadaomi Takenawa
    Lead, Elsevier BV, Jun. 2000, Journal of Biological Chemistry, 275(25) (25), 19389 - 19394
    [Refereed]
    Scientific journal

  • Tadaomi Takenawa, Toshiki Itoh, Kiyoko Fukami
    Apr. 1999, Chemistry and Physics of Lipids, 98(1-2) (1-2), 13 - 22, English
    [Refereed]
    International conference proceedings

  • Toshiki Itoh, Takeshi Ijuin, Tadaomi Takenawa
    Lead, Elsevier BV, Aug. 1998, Journal of Biological Chemistry, 273(32) (32), 20292 - 20299
    [Refereed]
    Scientific journal

  • Haiyan Yu, Kiyoko Fukami, Toshiki Itoh, Tadaomi Takenawa
    Elsevier BV, Aug. 1998, Experimental Cell Research, 243(1) (1), 113 - 122
    [Refereed]
    Scientific journal

  • Toshiaki Sakisaka, Toshiki Itoh, Kenji Miura, Tadaomi Takenawa
    American Society for Microbiology, 1997, Molecular and Cellular Biology, 17(7) (7), 3841 - 3849, English
    [Refereed]
    Scientific journal

  • Toshiki Itoh, Kenji Miura, Hiroaki Miki, Tadaomi Takenawa
    Lead, Elsevier BV, Nov. 1996, Journal of Biological Chemistry, 271(44) (44), 27931 - 27935
    [Refereed]
    Scientific journal

■ MISC
  • 【脂質ワールド】 細胞膜と脂質 細胞膜の曲率と張力をめぐる分子機構
    Itoh Toshiki
    Jun. 2016, 生体の科学, 67(3号) (3号), 214 - 219, Japanese

  • IRBITはphosphatidylinositol phosphate kinasesの活性中心と結合する
    安東英明, 廣瀬松美, GAINCHE Laura, 河合克宏, BONNEAU Benjamin, 伊集院壮, 伊藤俊樹, 竹縄忠臣, 御子柴克彦
    2015, 日本生化学会大会(Web), 88th

  • Microvillar tip-localized interaction between IRSp53 and PI(4,5)P2 drives brush border assembly in kidney epithelial cells.
    S. Kurisu, T. Itoh, T. Takenawa
    Dec. 2014, MOLECULAR BIOLOGY OF THE CELL, 25, English
    Summary international conference

  • イノシトールリン脂質代謝を制御するPH domainタンパク質の同定と機能解析
    水野稜子, 李翠芳, 小倉尚也, 加藤彩香, 喜多綾子, 佐藤亮介, 奥公秀, 阪井康能, 伊藤俊樹, 杉浦麗子
    2014, 日本薬理学会近畿部会プログラム・要旨集, 126th, 38, Japanese

  • イノシトールリン脂質代謝に関わる新規因子群の機能解析
    小倉尚也, 李翠芳, 喜多綾子, 加藤彩香, 水野稜子, 佐藤亮介, 奥公秀, 阪井康能, 伊藤俊樹, 杉浦麗子
    2014, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 3P-0306 (WEB ONLY), Japanese

  • 脂質二重層の曲率を認識する分子機構
    Itoh Toshiki
    2014, 医学のあゆみ・生命を支える脂質~最新の研究と臨床~, 248(13) (13), 1069 - 1074, Japanese

  • PHドメインタンパク質Sio1とイノシトールリン脂質シグナルの関わり
    小倉尚也, 李翠芳, 喜多綾子, 橋本佑香, 井原美沙子, 加藤彩香, 奥公秀, 伊藤俊樹, 阪井康能, 杉浦麗子
    2013, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2P-0462 (WEB ONLY), Japanese

  • 低分子量Gタンパク質Rab GTPaseよるイノシトールリン脂質シグナル伝達経路の空間的制御機構
    李翠芳, 橋本佑香, 井原美沙子, 加藤彩香, 小倉尚也, 奥公秀, 伊藤俊樹, 阪井康能, 杉浦麗子
    2013, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2P-0463 (WEB ONLY), Japanese

  • エンドサイトーシスにおける細胞膜の形状制御機構
    Itoh Toshiki
    Jan. 2012, 生化学, 84巻, 1, pp. 5-17, Japanese
    [Refereed]

  • リゾホスファチジルイノシトール特異的脂肪酸転移酵素LPIAT1の機能解析
    李 賢哲, 井上 貴雄, 佐々木 純子, 中崎 康子, 服部 光治, 田中 史晴, 宇田川 理, 河野 望, 伊藤 俊樹, 小木曽 英夫, 田口 良, 佐々木 雄彦, 新井 洋由
    (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 2P - 0100, Japanese

  • 22pJD-3 Mechanisms for the control and recognition of membrane curvature
    Itoh Toshiki
    The Physical Society of Japan (JPS), 24 Aug. 2011, Meeting abstracts of the Physical Society of Japan, 66(2) (2), 316 - 316, Japanese

  • 細胞膜で発現する細胞機能のダイナミズム SH3YL1は新規イノシトールリン脂質結合ドメインを介してdorsal ruffleの形成を制御する(Dynamics of cell functions at the plasma membrane SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain)
    伊藤 俊樹, 長谷川 純矢, 徳田 恵美, 竹縄 忠臣
    (一社)日本細胞生物学会, May 2011, 日本細胞生物学会大会講演要旨集, 63回, 92 - 92, English

  • SH3YL1はPI(3,4)P2産生を介して細胞膜rufflingの形成を制御している
    長谷川 純矢, 徳田 恵美, 澤井 治子, 竹縄 忠臣, 伊藤 俊樹
    日本脂質生化学会, Apr. 2011, 脂質生化学研究, 53, 121 - 124, Japanese

  • Dynamic interaction of amphiphysin with N-WASP regulates actin assembly
    山田浩司, PADILLA-PARRA Sergi, 朴宣奏, 朴宣奏, 伊藤俊樹, CHAINEAU Mathilde, CHAINEAU Mathilde, MONALDI Ilaria, CREMONA Ottavio, BENFENATI Fabio, CAMILLI Pietro De, COPPEY-MOISAN Maiete, TRAMIER Marc, GALLI Thierry, GALLI Thierry, 竹居孝二
    2011, 岡山医学会雑誌, 123(1) (1)

  • 【
    Itoh Toshiki
    Dec. 2010, 実験医学, 28巻, 20, pp. 3275-3278, Japanese

  • SH3YL1はPI(3,4)P2産生を介して細胞膜rufflingの形成を制御している(SH3YL1 regulates membrane ruffles through phosphoinositide metabolism)
    長谷川 純矢, 徳田 恵美, 澤井 治子, 竹縄 忠臣, 伊藤 俊樹
    (一社)日本細胞生物学会, May 2010, 日本細胞生物学会大会講演要旨集, 62回, 134 - 134, English

  • Hiroshi Yamada, Sergi Padilla-Parra, Sun-Joo Park, Toshiki Itoh, Mathilde Chaineau, Ilaria Monaldi, Ottavio Cremona, Fabio Benfenati, Pietro De Camilli, Maite Coppey-Moisan, Marc Tramier, Kohji Takei
    2010, NEUROSCIENCE RESEARCH, 68, E136 - E136, English
    Summary international conference

  • リゾホスファチジルイノシトール特異的脂肪酸転移酵素mboa-7/LPIATの哺乳類における機能解析
    中崎 康子, 井上 貴雄, 李 賢哲, 佐々木 純子, 田中 史晴, 宇田川 理, 河野 望, 服部 光治, 小木曽 英夫, 田口 良, 伊藤 俊樹, 佐々木 雄彦, 新井 洋由
    (公社)日本生化学会, Sep. 2009, 日本生化学会大会プログラム・講演要旨集, 82回, 2P - 074, Japanese

  • SH3YL1はPI(3,4)P2産生を介して細胞膜rufflingの形成を制御している
    長谷川 純矢, 徳田 恵美, 澤井 治子, 竹縄 忠臣, 伊藤 俊樹
    (公社)日本生化学会, Sep. 2009, 日本生化学会大会プログラム・講演要旨集, 82回, 2T18p - 11, Japanese

  • FerはPLD-PA経路の下流で働く膜曲率依存性チロシンキナーゼであり細胞運動に必須の役割を担う(Fer is a membrane curvature-dependent tyrosine kinase downstream of PLD-PA pathway essential for cell migration)
    伊藤 俊樹, 長谷川 純矢, 竹縄 忠臣
    (一社)日本細胞生物学会, May 2009, 日本細胞生物学会大会講演要旨集, 61回, 205 - 205, English

  • 生体膜の曲率依存的な細胞内情報伝達機構
    Itoh Toshiki
    Sep. 2008, 生体の科学・現代医学 生物学の仮説 学説2008, 59巻, 5, pp. 370-371, Japanese

  • Nano-LC-MS/MSシステムを用いた酸性リン脂質結合タンパク質の同定
    辻田 和也, 伊藤 俊樹, 尾山 大明, 竹縄 忠臣
    05 Jun. 2008, 脂質生化学研究, 50, 38 - 39, Japanese

  • Ferチロシンキナーゼと生体膜の相互作用
    伊藤 俊樹, 竹縄 忠臣
    05 Jun. 2008, 脂質生化学研究, 50, 328 - 331, Japanese

  • 癌浸潤転移における細胞運動のメカニズム 浸潤突起形成の分子メカニズム(Molecular mechanisms of cell migration in cancer invasion and metastasis Sequential signals toward podosome formation in NIH-src cells)
    及川 司, 伊藤 俊樹, 竹縄 忠臣
    (一社)日本細胞生物学会, Jun. 2008, 日本細胞生物学会大会講演要旨集, 60回, 94 - 94, English

  • 浸潤突起形成の分子メカニズム(Sequential signals toward podosome formation in NIH-src cells)
    及川 司, 伊藤 俊樹, 竹縄 忠臣
    (一社)日本細胞生物学会, Jun. 2008, 日本細胞生物学会大会講演要旨集, 60回, 166 - 166, English

  • Tks5/FISHはPtdIns(3,4)P2とPtdIns(3,4,5)P3が豊富な局所接着部(focal adhesion)へ自己分子を局在化させることによりpodosome形成を開始させる(Tks5/FISH initiates podosome formation by localizing itself to PtdIns(3,4)P2- and PtdIns(3,4,5)P3-enriched focal adhesions)
    及川 司, 伊藤 俊樹, 竹縄 忠臣
    日本発生生物学会・日本細胞生物学会, May 2007, 日本発生生物学会・日本細胞生物学会合同大会要旨集, 40回・59回, 131 - 131, English

  • PI3Kおよび関連シグナル伝達分子の機能 癌細胞におけるD3-ホスホイノシチドの定量化と視覚化のためのホスホイノシチド結合ドメインの利用(Use of phosphoinositide-binding domains for the quantification and visualization of D3-phosphoinositides in cancer cells)
    伊藤 俊樹, 及川 司, 辻田 和也, 竹縄 忠臣
    日本発生生物学会・日本細胞生物学会, May 2007, 日本発生生物学会・日本細胞生物学会合同大会要旨集, 40回・59回, 15 - 15, English

  • 細胞の形の制御 8.生体膜の形状を決定するタンパク質―アクチン細胞骨格制御におけるその役割
    ITOH TOSHIKI
    Aug. 2006, 実験医学, 24(13) (13), 1914 - 1923,1858(3),1858(5), Japanese

  • タンパク質相互作用を解明する最適メソッド タンパク質‐脂質間結合の検出
    FURUTANI MASAHIRO, ITOH TOSHIKI
    羊土社, Nov. 2005, バイオテクノロジージャーナル, 5(6) (6), 698 - 703, Japanese

  • The FCH plus coiled coil domain; a BAR-related, novel membrane tubulating domain conserved among dynamin-binding proteins
    Toshiki Itoh, Aurelien Roux, Pietro De Camilli
    Jun. 2005, CELL STRUCTURE AND FUNCTION, 30, 24 - 24, English
    Summary international conference

  • Racによるlamellipodia形成におけるWAVE2とPtdIns(3,4,5)P3の関わり
    及川 司, 末次 志郎, 伊藤 俊樹, 山口 英樹, 竹縄 忠臣
    (一社)日本細胞生物学会, May 2003, 日本細胞生物学会大会講演要旨集, 56回, 23 - 23, Japanese

  • リン脂質によるタンパク質活性制御 細胞内小胞輸送におけるタンパク質‐脂質間相互作用
    ITOH TOSHIKI, TAKENAWA TADAOMI
    Nov. 2002, 実験医学, 20(16) (16), 2315 - 2321, Japanese

  • ITOH TOSHIKI
    The Biophysical Society of Japan General Incorporated Association, Jun. 2002, 生物物理, 42(3) (3), 131 - 134, Japanese

  • ITOH TOSHIKI
    The cytoskeleton and the plasma membrane are two major components that define cellular shape, and control cell movement. The actin cytoskeleton lies just beneath the plasma membrane suggesting regulatory mechanisms based upon direct interactions between them. In fact, almost all of actin regulating proteins are known to bind phospholipids, especially phosphoinositides, to enhance or to suppress their activity. Such examples include the "classical" actin regulating proteins (profilin, gelsolin etc.) as well as recently unveiled ERM proteins and WASP families. In addition, interference of interaction between phosphoinositide and those proteins by a specific antibody or a phosphoinositide-binding peptide results in an inhibition of actin polymerization in response to extracellular stimuli. Furthermore, disturbance of intracellular phosphoinositide content by overexpression of phosphoinositide kinases or phosphatases affects the structure of actin cytoskeleton. These data clearly indicate the close relationship between phosphoinositide and actin cytoskeleton, and suggest the existence of the regulatory mechanism of cytoskeleton by phosphoinositide metabolizing enzymes. This review will focus on actin regulating proteins controlled by phosphoinositides and discuss their roles for cytoskeletal rearrangements upon extracellular signals.
    THE MEMBRANE SOCIETY OF JAPAN, Mar. 2002, 膜, 27(2) (2), 74 - 82, Japanese

  • エンドサイトーシスにおけるENTHドメインの役割
    ITOH TOSHIKI
    Jun. 2001, 実験医学, 19(8) (8), 970 - 972, Japanese

  • ENTHドメインとホスファチジルイノシトール4, 5-二リン酸の結合機構の解析
    伊藤 俊樹, 竹縄 忠臣
    10 May 2001, 脂質生化学研究, 43, 114 - 117, Japanese

  • プロテオーム研究とシグナル蛋白ドメイン 次世代のシグナル伝達研究 第2章 シグナリングを担うドメイン構造とその機能 6) その他のドメイン 2 脂質結合ドメインを介したイノシトールリン脂質の機能発現 PH・ENTHドメイン,FYVEフィンガー
    ITOH TOSHIKI
    Nov. 2000, 実験医学, 18(18) (18), 2607 - 2615, Japanese

  • Roles for phospholipids in spacio-temporal regulation and coordination of signal transduction.
    ITOH TOSHIKI, TAKENAWA TADAOMI
    Jan. 2000, 実験医学, 18(2) (2), 197 - 202, Japanese

  • Functional analysis of gene. Protein detection method : Peculiar detection method of protein by Western blotting and far-Western method.
    ITOH TOSHIKI
    Sep. 1999, 実験医学, 179 - 184, Japanese

  • Phosphatidylinositol Kinase: Functional Roles for PI4-Kinase and PIP Kinase in Signal Transduction.
    ITOH TOSHIKI, TAKENAWA TADAOMI
    共立出版, Jun. 1999, 蛋白質 核酸 酵素, 44(8) (8), 949 - 960, Japanese

  • Autophosphorylation of PIP kinase regulates its lipid kinase activity
    ITOH Toshiki, ISHIHARA Hisamitsu, SHIBASAKI Yoshikazu, OKA Yoshitomo, TAKENAWA Tadaomi
    01 Dec. 1998, 日本分子生物学会年会プログラム・講演要旨集, 21, 536 - 536, Japanese

  • New phosphatidylinositol-5-phosphate. 4-kinase exists locally in the endoplasmic reticulum and functions by phosphorylation.
    伊藤俊樹, 伊集院壮, 竹縄忠臣
    1998, 脂質生化学研究, 40

  • cDNA cloning of a novel phosphatidylinositol 4-phosphate 5-kinase and analysis of its intracellular localization.
    伊藤俊樹, 伊集院壮, 竹縄忠臣
    1997, 日本分子生物学会年会プログラム・講演要旨集, 20th

  • Ash/Grb2結合蛋白質p150のクローニングと機能解析
    匂坂 敏朗, 伊藤 俊樹, 高橋 京子, 竹縄 忠臣
    01 Aug. 1996, 日本分子生物学会年会プログラム・講演要旨集, 19, 521 - 521, Japanese

  • Regulation of actin cytoskeleton through phosphoinositide.
    ITOH TOSHIKI
    Aug. 1996, 実験医学, 14(14) (14), 2042 - 2049, Japanese

  • Western blotting for specific detection of proteins.
    ITOH TOSHIKI
    Apr. 1996, 実験医学, 222 - 226, Japanese

■ Books And Other Publications
  • リッピンコットシリーズ イラストレイテッド細胞分子生物学 / 第3章 生体膜、第4章 細胞骨格
    Itoh Toshiki
    Joint translation, 丸善出版, 2012, Japanese
    Textbook

  • タンパク質実験ハンドブック / タンパク質実験ハンドブック
    Takenawa Tadaomi, Itoh Toshiki
    Joint editor, 羊土社, 2010, Japanese
    Scholarly book

■ Lectures, oral presentations, etc.
  • DA-Rafは細胞膜と活性化Rasに結合することによりRas-ERK経路の全体的抑制因子として機能する
    高野和儀, 辻田和也, 伊藤俊樹, 遠藤剛
    日本生化学会大会(Web), 2021

  • Regulation of Cell Membrane Tension by Membrane Curvature-Inducing Proteins
    辻田和也, 伊藤俊樹
    日本細胞生物学会大会(Web), 2021

  • 67kDaラミニンレセプターはビタミンEとの結合によりパルミトイル化修飾を受ける
    岡本 聖香, 林 大輝, 足立 直子, Varnavas Mouchlis, 上田 修司, 山之上 稔, Dennis Edward, 斎藤 尚亮, 伊藤 俊樹, 白井 康仁
    日本生化学会大会プログラム・講演要旨集, Sep. 2020, Japanese, (公社)日本生化学会

  • 生体膜の変形が制御するバイオロジー 膜曲率誘導タンパク質による細胞膜の張力恒常性維持機構
    辻田 和也, 伊藤 俊樹
    日本生化学会大会プログラム・講演要旨集, Sep. 2020, Japanese, (公社)日本生化学会

  • 細胞接着と細胞膜から見たメカノ細胞生物学 細胞膜張力と膜変形タンパク質によるがん細胞運動・浸潤の制御
    辻田 和也, 伊藤 俊樹
    日本細胞生物学会大会講演要旨集, Jun. 2020, Japanese, (一社)日本細胞生物学会

  • 中分子創薬研究のフロンティア:〜生体分子の反応集積場としての膜曲率の役割〜 がん細胞運動 細胞膜張力と膜曲率誘導タンパク質によるがん細胞運動の制御
    辻田 和也, 伊藤 俊樹
    日本薬学会年会要旨集, Mar. 2020, Japanese, (公社)日本薬学会

  • Cancer cell migration: Regulation of cancer cell migration by plasma membrane tension and membrane curvature-inducing proteins
    辻田和也, 伊藤俊樹
    日本薬学会年会要旨集(CD-ROM), 2020

  • メカノバイオロジー研究の新展開-"力"による生命現象制御の理解深化に向けて- がん細胞運動のメカノバイオロジー
    辻田 和也, 伊藤 俊樹
    日本生化学会大会プログラム・講演要旨集, Sep. 2019, Japanese, (公社)日本生化学会

  • 生体膜脂質に関連する細胞現象の解析 リン脂質結合タンパク質SH3YL1の機能解析
    伊藤 俊樹, 山本 光, ジェブリ・イメン
    日本組織細胞化学会総会・学術集会講演プログラム・予稿集, Sep. 2019, Japanese, 日本組織細胞化学会

  • The Dynamic Changes in PI(4,5)P2 and PI(3,4,5)P3 are Required for the Elimination of RasG12V Transformed Cells by Cell Competition
    閻露, 伊藤俊樹
    日本分子生物学会年会プログラム・要旨集(Web), 2019

  • 細胞膜のダイナミックな挙動 細胞死におけるSH3YL1のミトコンドリア移行
    伊藤 俊樹, 山本 光
    日本生化学会大会プログラム・講演要旨集, Sep. 2018, Japanese, (公社)日本生化学会

  • 細胞膜リン脂質動態の生理と病態 細胞膜張力と膜変形タンパク質によるがんの浸潤・転移の制御機構
    辻田 和也, 伊藤 俊樹
    日本生化学会大会プログラム・講演要旨集, Sep. 2018, Japanese, (公社)日本生化学会

  • Zドリフトコンペンセーターを用いた細胞膜辺縁部の動態観察
    ITOH TOSHIKI
    日本組織細胞化学会総会・学術集会講演プログラム・予稿集, Sep. 2018, Japanese
    Oral presentation

  • 細胞死におけるSH3YL1のミトコンドリア移行
    TOSHIKI ITOH, YAMAMOTO HIKARU
    日本生化学会大会(Web), 2018, Japanese
    Oral presentation

  • 細胞膜変形タンパク質による細胞運動の極性制御機構
    Itoh Toshiki
    ConBio2017, Dec. 2017, Japanese, 生命系学会合同, 神戸, Domestic conference
    [Invited]
    Invited oral presentation

  • 細胞膜張力の恒常性制御機構
    Tsujita Kazuya, Itoh Toshiki
    ConBio2017, Dec. 2017, Japanese, 日本分子生物学会・日本生化学会, 神戸, Domestic conference
    [Invited]
    Invited oral presentation

  • 細胞競合 新たながん予防的治療法の開発を目指して(英語)
    藤田恭之, Itoh Toshiki
    日本癌学会総会記事, Sep. 2017, Japanese
    Oral presentation

  • 細胞競合における細胞膜張力の役割
    Itoh Toshiki
    第76回日本癌学会学術総会, Sep. 2017, Japanese, 日本癌学会, 横浜, Domestic conference
    [Invited]
    Invited oral presentation

  • 細胞死におけるSH3YL1の機能解析
    山本光, Itoh Toshiki
    第69回日本細胞生物学会大会, Jun. 2017, Japanese, 日本細胞生物学会, 仙台, Domestic conference
    Poster presentation

  • 細胞膜変形タンパク質によるアクチン重合と細胞運動の制御
    ITOH TOSHIKI
    日本解剖学会総会・全国学術集会講演プログラム・抄録集, 2017, Japanese
    Oral presentation

  • 膜変形タンパク質による細胞膜の張力を介した細胞運動の制御
    辻田和也, Itoh Toshiki
    日本生化学会大会プログラム・講演要旨集 89回, Sep. 2016, Japanese
    Oral presentation

  • The elucidation of the mechanism of lentinan-induced inflammatory suppression by visualizimg TNFR1 on the membrane
    SAKAGUCHI KANA, HASHIMOTO TAKASHI, ITO TOSHIKI, SHIRAI YASUHIDE, MIZUNO MASASHI
    Functional and Medical Foods for Chronic Diseases: Bioactive Compounds and Biomarkers, Sep. 2016, English, Harvard Medical School, International conference
    Poster presentation

  • レンチナンによって誘導されるTNFR1発現変化の可視化による炎症抑制機構の解明
    SAKAGUCHI KANA, HASHIMOTO TAKASHI, ITO TOSHIKI, SHIRAI YASUHITO, MIZUNO MASASHI
    日本食品科学工学会第63回大会, Aug. 2016, Japanese, 名城大学, Domestic conference
    Oral presentation

  • リン脂質結合タンパク質を介した細胞膜張力のシグナリング
    Itoh Toshiki, Tsujita Kazuya
    第88回日本生化学会ワークショップ, Dec. 2015, Japanese, 日本生化学会, 神戸, Domestic conference
    [Invited]
    Nominated symposium

  • イノシトールリン脂質代謝に関わる新規因子群の機能解析
    小倉 尚也, 水野 稜子, 李 翠芳, 喜多 綾子, 佐藤 亮介, 西口 英里, Itoh Toshiki, 杉浦 麗子
    第38回日本分子生物学会年会、第88回日本生化学会大会合同大会, Dec. 2015, Japanese, 日本生化学会・日本分子生物学会, 神戸, Domestic conference
    Poster presentation

  • Role of membrane-bending proteins in cell polarity formation
    Itoh Toshiki
    2015 ASCB Annual Meeting, Dec. 2015, English, American Society for Cell Biology, San Diego, USA, International conference
    [Invited]
    Invited oral presentation

  • Membrane Tension Signaling Mediated by Lipid-binding Proteins
    Itoh Toshiki, Tsujita Kazuya
    第38回日本分子生物学会年会、第88回日本生化学会大会合同大会, Dec. 2015, Japanese, 日本生化学会・日本分子生物学会, 神戸, Domestic conference
    Oral presentation

  • IRBITはphosphatidylinositol phosphate kinasesの活性中心と結合する
    安東 英明, 廣瀬 松美, Laura Gainche, 河合 克宏, Benjamin Bonneau, Ijuin Takeshi, Itoh Toshiki, 竹縄 忠臣, 御子柴 克彦
    第38回日本分子生物学会年会、第88回日本生化学会大会合同大会, Dec. 2015, Japanese, 日本生化学会・日本分子生物学会, 神戸, Domestic conference
    Poster presentation

  • F-BAR domain proteins and actin cytoskeleton
    Itoh Toshiki
    UCSD-KU meeting “Comprehensive Understanding of the Roles of Lipids in the Life Sciences”, Dec. 2015, English, University of California San Diego, La Jolla, USA, International conference
    [Invited]
    Invited oral presentation

  • 細胞膜の幾何学と物理学にもとづく細胞運動の理解
    TOSHIKI ITOH
    生物物理(Web), Aug. 2015, Japanese
    Oral presentation

  • 細胞運動時の極性形成における細胞膜の張力と膜変形タンパク質のフィードバック調節機構
    Tsujita Kazuya, Itoh Toshiki
    第67回日本細胞生物学会, Jul. 2015, Japanese, 日本細胞生物学会, 東京, Domestic conference
    Public symposium

  • 細胞内ホスファチジン酸産生を時・空間的に解析できる簡便かつ新規な可視化プローブの開発
    沖本航, 中井寛子, Itoh Toshiki, 森田真也, 上田修司, 山之上稔, 白井康仁
    脂質生化学研究, May 2015, Japanese
    Oral presentation

  • Membrane tension sensing by an F-BAR protein for cell migration
    Itoh Toshiki
    Invited seminar, Apr. 2015, English, Seoul National University, Seoul, 韓国, International conference
    [Invited]
    Invited oral presentation

  • Formin binding protein 17 is a membrane tension sensor involved in polarity formation during cell migration
    Itoh Toshiki
    International Symposium on Nanomedicine and Biomedical Sciences, Apr. 2015, English, Ajou University, Suwon, 韓国, International conference
    [Invited]
    Invited oral presentation

  • 脂質結合ドメインを用いた新規ホスファチジン酸可視化プローブの開発
    OKIMOTO KO, NAKAI HIROKO, ITOH TOSHIKI, UEDA SHUJI, YAMANOUE MINORU, SHIRAI YASUHITO
    日本農芸化学会関西支部講演会講演要旨集, Dec. 2014, Japanese
    Oral presentation

  • イノシトールリン脂質代謝に関わる新規因子群の機能解析
    小倉 尚也, 李 翠芳, 喜多 綾子, 加藤 彩香, 水野 稜子, 佐藤 亮介, 奥 公秀, 阪井 康能, Itoh Toshiki, 杉浦 麗子
    第37回日本分子生物学会年会, Dec. 2014, Japanese, 日本分子生物学会, 横浜, Domestic conference
    Poster presentation

  • F-BARドメインタンパク質による細胞運動の制御
    Itoh Toshiki, Tsujita Kazuya
    第87回日本生化学会大会, Oct. 2014, Japanese, 日本生化学会, 京都, Domestic conference
    Oral presentation

  • 細胞質型チロシンキナーゼFerと生体膜との相互作用の解析
    Itoh Toshiki, 山本 光, Tsujita Kazuya
    第56回日本脂質生化学会, Jun. 2014, Japanese, 日本脂質生化学会, 大阪, Domestic conference
    Oral presentation

  • I-BARドメインの膜変形活性による腎刷子縁の形成メカニズム
    栗栖 修作, Itoh Toshiki, Takenawa Tadaomi
    第56回日本脂質生化学会, Jun. 2014, Japanese, 日本脂質生化学会, 大阪, Domestic conference
    Oral presentation

  • F-BARタンパク質による細胞膜の張力を介した極性形成機構
    Tsujita Kazuya, Itoh Toshiki
    第56回日本脂質生化学会, Jun. 2014, Japanese, 日本脂質生化学会, 大阪, Domestic conference
    Oral presentation

  • イノシトールリン脂質代謝を制御するPH domainタンパク質の同定と機能解析
    MIZUNO RYOKO, RI SUIHO, OGURA NAOYA, KATO AYAKA, KITA AYAKO, SATO RYOSUKE, OKU MASAHIDE, SAKAI YASUYOSHI, ITOH TOSHIKI, SUGIURA REIKO
    日本薬理学会近畿部会プログラム・要旨集, 2014, Japanese
    Oral presentation

  • 脂質膜内微小ドメインを足場として進む膜変形モジュールタンパク質の自己組織化反応
    MOTEGI TOSHINORI, TAKIGUCHI KINGO, TAKIGUCHI YOKO, ITOH TOSHIKI, TERO RYUGO
    表面科学学術講演会講演要旨集, Nov. 2013, Japanese
    Oral presentation

  • 生体膜リン脂質研究の最前線 脂質結合モジュールによる生体膜の形状制御
    Itoh Toshiki
    日本生化学会大会プログラム・講演要旨集 86回, Sep. 2013, Japanese
    Oral presentation

  • 酸性リン脂質研究の最前線 分極化アクチン重合に必要な膜張力へのFBP17応答の自己組織化(Self-organization of FBP17 responds to membrane tension required for polarized actin polymerization)(英語)
    辻田和也, Itoh Toshiki
    日本生化学会大会プログラム・講演要旨集 86回, Sep. 2013, Japanese
    Oral presentation

  • F-BAR蛋白質による膜突起形成反応のリアルタイムイメージング解析
    滝口陽子, Itoh Toshiki, 辻田和也, 柳澤美穂, 藤原慶, 山本暁久, 市川正敏, 山田駿介, 滝口金吾
    日本細胞生物学会大会講演要旨集 65回, May 2013, Japanese
    Oral presentation

  • F‐BARドメイン蛋白質による膜突起形成過程のリアルタイムイメージング解析
    TAKIGUCHI YOKO, ITOH TOSHIKI, TSUJITA KAZUYA, YANAGISAWA MIHO, FUJIWARA KEI, YAMAMOTO AKIHISA, ICHIKAWA MASATOSHI, YAMADA SHUNSUKE, TERO RYUGO, TAKIGUCHI KINGO
    日本膜学会年会講演要旨集, May 2013, Japanese
    Oral presentation

  • 低分子量Gタンパク質Rab GTPaseよるイノシトールリン脂質シグナル伝達経路の空間的制御機構
    RI SUIHO, RI SUIHO, HASHIMOTO YUKA, IHARA MISAKO, KATO AYAKA, OGURA NAOYA, ITOH TOSHIKI, 阪井康能, SAKAI YASUYOSHI
    日本分子生物学会年会プログラム・要旨集(Web), 2013, Japanese
    Oral presentation

  • 脂質結合モジュールによる生体膜の形状制御
    ITOH TOSHIKI
    日本生化学会大会(Web), 2013, Japanese
    Oral presentation

  • PHドメインタンパク質Sio1とイノシトールリン脂質シグナルの関わり
    OGURA NAOYA, RI SUIHO, RI SUIHO, KITA AYAKO, HASHIMOTO YUKA, IHARA MISAKO, KATO AYAKA, ITOH TOSHIKI, 阪井康能, SAKAI YASUYOSHI
    日本分子生物学会年会プログラム・要旨集(Web), 2013, Japanese
    Oral presentation

  • 生体膜の形状変化を誘導、感知するタンパク質の機能
    Itoh Toshiki
    第16回ペプチドフォーラム, Dec. 2012, Japanese, 日本ペプチド学会, 京都大学宇治キャンパス宇治おうばくプラザ, Domestic conference
    [Invited]
    Invited oral presentation

  • Membrane curvature regulation by lipid-binding proteins
    Itoh Toshiki
    第85回 日本生化学会大会, Dec. 2012, English, 日本生化学会, 福岡国際会議場, Domestic conference
    [Invited]
    Invited oral presentation

  • Antagonistic regulation of F-BAR protein assemblies for podosome formation
    Itoh Toshiki
    2nd POSTECH International Symposium on Bio-Imaging, Nov. 2012, English, Pohang University of Science and Technology, Pohang University of Science and Technology, Pohang, Korea, International conference
    [Invited]
    Invited oral presentation

  • 生体膜の形状制御に関与するタンパク質の機能
    Itoh Toshiki
    第54回 日本脂質生化学会, Jun. 2012, Japanese, 日本脂質生化学会, 九州大学医学部百年講堂, Domestic conference
    [Invited]
    Invited oral presentation

  • The SYLF domain, a novel phosphoinositide-binding module involved in the formation of circular dorsal ruffles
    Itoh Toshiki
    Kobe University-University of Washington Joint Symposium on Integrative Membrane Biology and Signal Transduction Medicine, Dec. 2011, English, 神戸, International conference
    Invited oral presentation

  • 生体膜の曲率を制御・感知する分子機構
    Itoh Toshiki
    日本物理学会2011年秋季大会, Sep. 2011, Japanese, 富山, Domestic conference
    Invited oral presentation

  • 新規リン脂質結合ドメインによる生体膜形状制御
    Itoh Toshiki
    第11回日本蛋白質科学会年会, Jun. 2011, Japanese, 大阪, Domestic conference
    Invited oral presentation

  • SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide–binding domain
    Itoh Toshiki, 長谷川 純矢, 徳田 恵美, Takenawa Tadaomi
    第63回日本細胞生物学会大会, Jun. 2011, Japanese, 札幌, Domestic conference
    Invited oral presentation

  • Membrane curvature generation and sensing by lipid-binding domains
    Itoh Toshiki
    The 30th Naito Conference "Membrane Dynamics and Lipid Biology [II]: Domain, Droplet and Diseases", Jun. 2011, English, 札幌, International conference
    Invited oral presentation

  • 新規リン脂質結合ドメインによる生体膜形状制御
    ITOH TOSHIKI
    日本蛋白質科学会年会プログラム・要旨集, May 2011, Japanese
    Oral presentation

  • SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain
    HASEGAWA JUN'YA, TOKUDA EMI, SAWAI HARUKO, TAKENAWA TADAOMI, ITOH TOSHIKI
    生化学, May 2011, Japanese
    Oral presentation

  • 蛋白質による膜突起形成過程のリポソームを用いたリアルタイムイメージング
    TAKIGUCHI KINGO, ITOH TOSHIKI, TERO RYUGO, TAKIGUCHI YOKO
    日本膜学会年会講演要旨集, Apr. 2011, Japanese
    Oral presentation

  • SH3YL1はPI(3,4)P2産生を介して細胞膜rufflingの形成を制御している
    HASEGAWA JUN'YA, TOKUDA EMI, SAWAI HARUKO, TAKENAWA TADAOMI, ITOH TOSHIKI
    脂質生化学研究, Apr. 2011, Japanese
    Oral presentation

  • Amphipathic α-helices in the generation and sensing of membrane curvature
    Itoh Toshiki
    2nd April Workshop on Membrane Biology at POSTECH, Apr. 2011, English, 浦項, 韓国, International conference
    Invited oral presentation

  • リゾホスファチジルイノシトール特異的脂肪酸転移酵素LPIAT1の機能解析
    LEE HYEON-CHEOL, INOUE TAKAO, INOUE TAKAO, SASAKI JUNKO, NAKASAKI YASUKO, HATTORI MITSUHARU, TANAKA FUMIHARU, UDAGAWA OSAMU, ITOH TOSHIKI, KONO NOZOMI, ITO TOSHIKI, OGISO HIDEO, TAGUCHI RYO
    生化学, 2011, Japanese
    Oral presentation

  • 脂質結合ドメインによる生体膜ダイナミクスの制御機構
    ITOH TOSHIKI, HASEGAWA JUN'YA, TAKENAWA TADAOMI, TAKIGUCHI KINGO, TAKIGUCHI YOKO
    日本蛋白質科学会年会プログラム・要旨集, May 2010, Japanese
    Oral presentation

  • 細胞膜の曲率依存的なFerチロシンキナーゼ活性制御機構の解明
    ITOH TOSHIKI
    日本応用酵素協会誌, Feb. 2010, Japanese
    Oral presentation

  • 細胞・組織内でのホスホイノシタイドの可視化
    Irino Yasuhiro, 徳田 恵美, Itoh Toshiki, Takenawa Tadaomi
    第82回日本生化学会大会, Oct. 2009, Japanese, 日本生化学会, 神戸, Domestic conference
    Oral presentation

  • Proteome of Acidic Phospholipid-binding Proteins: Spatial and Temporal Regulation of Coronin 1A by Phosphoinositides
    Tsujita Kazuya, Itoh Toshiki, Takenawa Tadaomi
    第82回生化学学会, Oct. 2009, Japanese, 日本生化学学会, 神戸, Domestic conference
    [Invited]
    Invited oral presentation

  • リゾホスファチジルイノシトール特異的脂肪酸転移酵素mboa‐7 LPIATの哺乳類における機能解析
    NAKASAKI YASUKO, INOUE TAKAO, INOUE TAKAO, LEE HYEON-CHEOL, SASAKI JUNKO, TANAKA FUMIHARU, UDAGAWA OSAMU, KONO NOZOMU, KONO NOZOMU, HATTORI MITSUHARU, ITOH TOSHIKI, TAGUCHI RYO, TAGUCHI RYO
    生化学, Sep. 2009, Japanese
    Oral presentation

  • SH3YL1はP1(3,4)P2産生を介して細胞膜rufflingの形成を制御している
    HASEGAWA JUN'YA, TOKUDA EMI, SAWAI HARUKO, TAKENAWA TADAOMI, ITOH TOSHIKI
    生化学, Sep. 2009, Japanese
    Oral presentation

  • 新規脂質結合ドメインを有するSH3YL1の機能解析
    HASEGAWA JUN'YA, TOKUDA EMI, SAWAI HARUKO, TAKENAWA TADAOMI, ITOH TOSHIKI
    脂質生化学研究, Jul. 2009, Japanese
    Oral presentation

  • 細胞・組織内でのホスホイノシタイドの可視化
    Irino Yasuhiro, 徳田 恵美, Itoh Toshiki, Takenawa Tadaomi
    第51回日本脂質生化学会, Jul. 2009, Japanese, 日本脂質生化学会, 名古屋, Domestic conference
    Oral presentation

  • 細胞外液層取り込みにおけるFerチロシンキナーゼの役割
    Itoh Toshiki, Takenawa Tadaomi
    第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, Dec. 2008, Japanese, 日本生化学会・日本分子生物学会, 神戸, Domestic conference
    Oral presentation

  • Roles of phosphoinositides in podosome/invadopodia formation
    Itoh Toshiki, Oikawa Tsukasa, Takenawa Tadaomi
    第67回日本癌学会学術総会, Oct. 2008, Japanese, 日本癌学会, 名古屋, Domestic conference
    Oral presentation

  • Fer tyrosine kinase induces lamellipodia formation through membrane binding
    Itoh Toshiki, Takenawa Tadaomi
    第60回日本細胞生物学会大会, Jul. 2008, English, 日本細胞生物学会, 横浜, Domestic conference
    Poster presentation

  • Ferチロシンキナーゼと生体膜の相互作用
    Itoh Toshiki, Takenawa Tadaomi
    第50回 日本脂質生化学会, Jun. 2008, Japanese, 日本脂質生化学会, 徳島, Domestic conference
    Oral presentation

  • Nano‐LC‐MS MSシステムを用いた酸性リン脂質結合タンパク質の同定
    TSUJITA KAZUYA, ITOH TOSHIKI, OYAMA MASAAKI, TAKENAWA TADAOMI
    脂質生化学研究, May 2008, Japanese
    Oral presentation

  • Ferチロシンキナーゼと生体膜の相互作用
    ITOH TOSHIKI, TAKENAWA TADAOMI
    脂質生化学研究, May 2008, Japanese
    Oral presentation

  • F-BAR domain, a membrane-tubulating module involved in endocytosis and cytoskeletal rearrangements
    Itoh Toshiki, Takenawa Tadaomi
    Annual Meeting 2008 of Korean Society for Biochemistry and Molecular Biology, May 2008, English, 韓国生化学・分子生物学会, ソウル, 韓国, International conference
    Invited oral presentation

  • PHドメインを有するタンパク質Slp2のイノシトールリン脂質シグナル伝達経路における役割
    Kuno Takayoshi, Itoh Toshiki, Sugiura Reiko
    第112回日本薬理学会近畿部会, Nov. 2007, Japanese, 日本薬理学会, 大阪, Domestic conference
    Oral presentation

  • Ferチロシンキナーゼによるリン脂質結合と生体膜の形状制御
    ITOH TOSHIKI, TAKENAWA TADAOMI
    生化学, 2007, Japanese
    Oral presentation

  • Recによるlamellipodia形成におけるWAVE2とPtdIns(3,4,5)P3の関わり
    OIKAWA TSUKASA, OIKAWA TSUKASA, TOSHIKI ITOH, SUETSUGU SHIRO, 竹縄忠臣
    日本細胞生物学会大会講演要旨集, 2003, Japanese
    Oral presentation

  • エンドソーム間輸送に関与する新規epsinファミリータンパク(KIAA0171)
    ITOH TOSHIKI, TAKENAWA TADAOMI
    生化学, Aug. 2002, Japanese
    Oral presentation

  • ENTHドメインとホスファチジルイノシトール4,5‐二リン酸の結合機構の解析
    ITOH TOSHIKI, TAKENAWA TADAOMI
    脂質生化学研究, May 2001, Japanese
    Oral presentation

  • エンドサイトーシスに関与するENTHドメインとイノシトールリン脂質の特異的結合
    ITOH TOSHIKI, TAKENAWA TADAOMI
    生化学, Aug. 2000, Japanese
    Oral presentation

  • ホスファチジルイノシトールーリン酸(PIP)キナーゼファミリーの自己リン酸化による活性制御機構
    ITOH TOSHIKI, ISHIHARA HISAMITSU, SHIBASAKI YOSHIKAZU, OKA YOSHITOMO, TAKENAWA TADAOMI
    日本分子生物学会年会プログラム・講演要旨集, Nov. 1998, Japanese
    Oral presentation

  • cDNA cloning of a novel phosphatidylinositol 4-phosphate 5-kinase and analysis of its intracellular localization.
    ITOH TOSHIKI, IJUIN TAKESHI, TAKENAWA TADAOMI
    日本分子生物学会年会プログラム・講演要旨集, Dec. 1997, Japanese
    Oral presentation

  • Association of Src Homology 2 Domains with .BETA.-Tubulin Independent of Tyrosine Phosphorylation.
    ITOH TOSHIKI, MIURA KENJI, MIKI HIROAKI, TAKENAWA TADAOMI
    日本分子生物学会年会プログラム・講演要旨集, Nov. 1995, Japanese
    Oral presentation

■ Affiliated Academic Society
  • THE JAPANESE CANCER ASSOCIATION

  • THE JAPANESE CONFERENCE ON THE BIOCHEMISTRY OF LIPIDS

  • JAPAN SOCIETY FOR CELL BIOLOGY

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

  • THE JAPANESE BIOCHEMICAL SOCIETY

■ Research Themes
  • Osteoclast fusion mechanism based on plasma membrane curvature and tension
    伊藤 俊樹
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2022 - 31 Mar. 2025

  • A feedback mechanism between the plasma membrane and the actin cytoskeleton underneath during cell migration
    Itoh Toshiki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2019 - 31 Mar. 2022
    In cell migration, the cytoskeleton exerts a driving force by stretching the plasma membrane by pushing it from the inside. A feedback mechanism that regulates the retraction of the extended plasma membrane is vital for efficient cell movement, but its molecular detail is unknown. In this study, we focused on a group of proteins that control and sense the tension applied to the plasma membrane with the activity of regulating the actin cytoskeleton. Our results reveal a part of the feedback mechanism between the plasma membrane and the actin cytoskeleton underneath during cell migration.

  • Itoh Toshiki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2016 - 31 Mar. 2019, Principal investigator
    In this study, we focus on the membrane tension which is a physical parameter related to the cell membrane. We aim to elucidate the molecular mechanism of mechano-signaling that controls "cell polarity" which plays an essential role in cell morphogenesis and physiological functions. By monitoring the intracellular localizations of inositol phospholipids that regulate the actin cytoskeleton, we found a characteristic localization of these lipids associated with epithelial cell carcinogenesis. Specifically, PI (3,4,5) P3, a PI3-kinase product, increased remarkably on the basal side of the plasma membrane, while PI (4,5) P2 was distributed all around the cancer cell membrane that deviated from the apical surface. Our findings also suggest that the tumor suppressor gene PTEN may play a role in the invasive phenomenon associated with epithelial cell carcinogenesis.
    Competitive research funding

  • Fujita Yasuyuki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Hokkaido University, 10 Jul. 2014 - 31 Mar. 2019
    The study has been steadily developed, and we have eventually acquired quite satifcatroy achievement. I will briefly summarized the main publications. 1) Identification of cell competition regulators (Anton et al., 2014, JCS; Ohoka et al., 2015, JCS); 2)Involvement of endocytosis in cell competition (Saitoh et al., 2017, PNAS); 3) Involvement of metabolism in cell competition (Kon et al., 2017, Nat Cell Biol); 4) Cell competition between normal and p53-mutated epithelial cells (Watanabe et al., 2018, Cell Rep); 5) Obesity suppresses apical elimination of RasV12-transformed cells through cell competition (Sasaki et al., 2018, Cell Rep)

  • KAWASAKI Masato, ITOH Toshiki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), High Energy Accelerator Research Organization, 01 Apr. 2015 - 31 Mar. 2018
    SYLF domain is a new member of membrane-deforming protein implicated in endocytosis. The crystal structure of SYLF domain of thermophilic bacteria Thermotoga maritima was determined at 2.2 angstrom resolution Based on the structure, a predicted loop region of human SYLF domain was deleted. The modified human SYLF domain could be crystallized and structure was determined at 2.0 angstrom resolution. SYLF domain adopts a novel fold and the basic surface patches were expected to interact with membrane.

  • Takenawa Tadaomi, ITOH Toshiki, IJUIN Takeshi, TSUJITA Kazuya, TOKUDA Emi, HASEGAWA Junya, IRINO Yasuhiro
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (S), Grant-in-Aid for Scientific Research (S), Kobe University, 01 Apr. 2011 - 31 Mar. 2016
    Phosphoinositides act as crucial lipids to regulate versatile functions in life. Phosphoinositide-binding proteins, FBP17, PSTPIP2, SH3YL1 and ARAP1 recognize and bind membrane curvature, resulting in membrane deformation, such as coated pits and vesiculation of membrane. PI(3,4,5)P3 5-phosphatase SKIP binds GRP78 in endoplasmic reticulum under resting condition. But in response to insulin, it moves to membranes where it associates with Pak1 and hydrolyses PI(3,4,5)P3 spatio-temporaly around insulin receptors. Sac1 PI4P 4-phosphatase controls the PI4P concentration in Golgi, which is involved in cell adhesion and tumor metastasis.Thus, decrease in PI4P in Golgi prevents the invasion and metastasis of cancer cells.
    Competitive research funding

  • Ｆｅｒチロシンキナーゼの天然変性領域を介した細胞膜結合による活性化機構
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 新学術領域研究(研究領域提案型), 新学術領域研究(研究領域提案型), 神戸大学, 01 Apr. 2012 - 31 Mar. 2015
    チロシンキナーゼは、細胞外からの情報分子を細胞内シグナルへと変換する過程、いわゆる細胞内情報伝達系における最も初期の段階で機能する酵素である。細胞膜貫通型チロシンキナーゼは細胞外の液性因子の受容体タンパク質として、膜タンパク質であるSrc型チロシンキナーゼは細胞外マトリックスへの細胞接着によって活性化されることで、それぞれ細胞の増殖や運動を司る。医療分野においてもさまざまなチロシンキナーゼ阻害薬が臨床応用されており、BCR-ABLやEGF受容体などを特異的に阻害する分子標的治療薬が注目を集めている。本研究では、細胞質型チロシンキナーゼFerに存在する特定の立体構造を取らない「天然変性」領域（以下FX tail）に着目し、細胞膜との直接的な相互作用による活性化機序の解明を目的としている。本年度も引き続き、FXtailの膜結合能に関する解析を行った。その結果、FXbodyを含むFXドメイン全体に比べて、FXtail領域のみからなるコンストラクトは強い膜結合能を示すことが分かった。また、FXtailのカルボキシル末端側に存在するSH2ドメインを含めたFX+SH2コンストラクトもFXドメインに比べて高い膜結合能を持つことが明らかとなった。この結果は、FXtailがFXbodyと相互作用することで通常は閉じたコンフォメーションを取っており、膜結合に伴って開いた形に構造変化を起こす可能性を示唆している。架橋剤を用いた分子間架橋実験により、FXドメインはリポソーム存在下においてのみ高分子量の多量体を形成していることを示唆するデータも得られた。以上の結果は、チロシンキナーゼFerが生体膜との結合によって活性化するメカニズムに関する有用な洞察を与えるものと考えられる。

  • ITOH TOSHIKI, TSUJITA Kazuya
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2012 - 31 Mar. 2015, Principal investigator
    It was found that human SH3YL1, which contains a novel phosphoinositide-binding domain named the SYLF domain, is involved in endocytosis of epidermal growth factor receptor. In vitro, SH3YL1 not only bound to liposomes, but also mediated interactions between liposomes that it resides, promoting aggregation of membrane vesicles. This study also succeeded in obtaining a knowledge about the positively-charged residues in the SYLF domain that participate in lipid-binding, therefore will provide a novel molecular basis of endocytosis.
    Competitive research funding

  • ANDO Hideaki, TAKENAWA Tadaomi, IJUIN Takeshi, ITOH Toshiki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up, Grant-in-Aid for Research Activity Start-up, The Institute of Physical and Chemical Research, 2009 - 2010
    We analyzed the interaction between IRBIT/Long-IRBIT and PIP kinase family. IRBIT specifically bound to PIPKIα in mouse brain and the interaction was direct. On the contrary, Long-IRBIT did not interacted with PIPKI. The interaction between IRBIT and PIPKIα was dependent on the phosphorylation sites of IRBIT and the catalytic amino acid of PIPKIα. Furthermore, in vitro lipid kinase assay suggested the possibility that IRBIT suppresses the activity of PIPKIα.

  • ITOH Toshiki
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B), Grant-in-Aid for Young Scientists (B), Kobe University, 2009 - 2010, Principal investigator
    Fer, a tyrosine kinase harboring membrane-bending F-BAR domain, was found to be activated in a manner dependent on membrane curvature. It was also revealed that Fer is involved in macropinocytosis mediated by membrane ruffle formation, as well as clathrin-mediated endocytosis for internalization of transferrin receptor.
    Competitive research funding

  • TAKENAWA Tadaomi, SASAKI Takehiko, ITOH Toshiki, IJUIN Takeshi, YAMAZAKI Daisuke
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Creative Scientific Research, Grant-in-Aid for Creative Scientific Research, 2006 - 2010
    We developed a new method to quantify and visualize phosphoinositides by the use of Q-dot labeled PH domains which recognize phosphoinositides with high affinity and specificity. By this method, three different phosphoinositides were quantified and visualized simultaneously. We found that FBP17 and CIP4 proteins have F-Bar domains that bind phosphoinositides and deform membranes. F-Bar domain forms a polymerized filament and changes plasma membrane to tube-like structure, resulting in the formation of invaginated pits. We also found a new phosphoinositide binding domain, SYLF domain in SH3YL1, which was involved in the formation of macropinocytosis.

  • 曲面としての細胞膜における膜の曲率依存的なシグナル伝達機構
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 神戸大学, 2007 - 2008
    Ferチロシンキナーゼのアミノ末端領域を用いて生体膜に対する結合アッセイを行ったところ、F-BAR/EFCドメイン(アミノ末端側300残基)よりもC末端側の270-445アミノ酸領域(ドメインX)において高い脂質結合能が見出された。直径の異なるリボソームを用いて結合アッセイを行ったところ、興味深いことに、F-BAR/EFCドメインは直径約1-10μm程度の大きなリボソーム(LMV)により強く結合したのに対し、隣接するドメインXは50-200nm程度の小さなリボソーム(SUV)に高い親和性を示した。すなわち、Ferのアミノ末端領域には二種類の異なる生体膜の曲率センサーが存在すると考えられた。次に、Ferのキナーゼ活性に対するリボソーム添加の影響を検討したところ、LMVは高濃度下でわずかにFerを活性化したのに対し、SUVは強い活性化能を有することが明らかとなった。この結果は、FerのドメインXを介した曲率の高い生体膜との相互作用がチロシンキナーゼの活性化に重要な役割を担うことを示しており、本課題が想定した「生体膜の曲率依存的なシグナル伝達機構」の存在を強く示唆するものであった。COS7細胞におけるGFP-Ferの過剰発現は、Vav2およびCortactinのチロシンリン酸化とそれに伴う葉状仮足(ラメリポディア)構造の形成を誘起した。F-BARドメインを欠損した変異体(Fer△F-BAR)、およびドメインXを欠損した変異体の過剰発現ではこのようなラメリポディアの形成は観察されなかった。以上の結果から、細胞膜の曲率依存的にFerが活性化され、Vav2(RacGEF)やCortactin(アクチン重合タンパク質)のチロシンリン酸化を通じたアクチン細胞重合を引き起こし、細胞の形態変化を誘導する分子モデルを打ち立てることに成功した。

  • エンドサイトーシスにおけるF-BARドメインの役割
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 2006 - 2007
    1.前年度までに明らかにした、FBP17のF-BARドメイン内における点突然変異L7E、F11EおよびH17Dについて、COS7細胞内への過剰発現実験を行った。野生型のFBP17タンパク質の過剰発現では、細胞の陥入によるチューブ状膜構造の形成が誘起されたのに対し、いずれの変異体もこれらの膜変形活性を失っていた。これは前年度に明らかにしたin vitroでの膜変形アッセイの結果を支持するものであり、FBP17のF-BARドメイン内においてリン脂質結合と膜変形それぞれに関与するアミノ酸の存在を示唆するものである。 2.前年度に確立したBARドメインとF-BARドメインの同一膜チューブ上への局在について、さらに多くのタンパク質を用いて検討を加えた。その結果、まずF-BARドメインを持つタンパク質については少なくとも(1)FBP17/CIP4サブファミリー(2)Syndapinサブファミリー、(3)PSTPIPサブファミリーの3つのグループが存在し、これらはCOS7細胞内での共発現によって誘導されるチューブ上において別個の局在を示すことが明らかとなった。さらにBARドメインタンパク質との詳細な局在比較から、意外なことにAmphiphysin (BAR)とPSTPIP(F-BAR)が高度に共局在することが明らかとなった。これらの結果は、同じF-BARドメインファミリー内においても、エンドサイトーシスのそれぞれのステップで異なる細胞膜の曲率を認識する、もしくは作り出すサブグループに分業化されることを示唆している。またF-BARファミリーとBARファミリーの間でも共通の膜曲率を認識するサブグループが在し、これらが特定の膜変形ステップにおいて協調的に作用すると考えられた。

  • F-BARドメインタンパクによる細胞膜の形状制御機構
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 2006 - 2007
    本年度はF-BAR/EFCドメインを持つチロシンキナーゼサブファミリーFerのアクチン骨格制御における役割を解析した。COS7細胞内にGFP-Ferを発現させるとlamellipodia構造を誘起し、この構造を優性不活性型Racの共発現によって抑制された。チロシンキナーゼ活性を持たないFer D742Rや自己リン酸化部位の変異体であるFer Y714Fではこのような現象は観察されなかった。興味深いことに、F-BAR/EFCドメインを欠損した変異体(Fer・F-BAR)においてもlamellipodia形成を誘起することは出来なかった。さらに、COS7細胞内にGFP-FerおよびMycタグを付加したCortactin(F-アクチン重合タンパク質)およびVav2(RacGEF)を共発現したところ、Ferのチロシンキナーゼ活性依存的なチロシンリン酸化が認められた。また、上述のようなGFP-Ferの過剰発現によって誘起されたlamellipodiaには、GFP-Ferと内在性Cortactinのリン酸化部位に対する特異的抗体(抗pTyr421)のシグナルが共局在することが観察された。 これらの結果はFerチロシンキナーゼがF-BARドメインを介したリン脂質との相互作用によって細胞膜に局在し、その形状を制御すると同時に(1)Cortactinのチロシンリン酸化によるRacの活性化、(2)Vav2のリン酸化によるRacの活性化を引き起こすことによってlamellipodia形成を誘導することを示唆している。

  • 細胞膜受容体のエンドサイトーシスによる細胞増殖制御機構の解明
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 特定領域研究, 特定領域研究, 東京大学, 2002 - 2002
    (1)AP180のENTHドメインがPI(4,5)P_2に最も強く結合することを確認した。その後、epsinにおいて脂質結合に必須である63番Arg、76番Lysにそれぞれ相当する各残基、66番Arg、77番LysをAlaに置換すると、PI(4,5)P2結合能を失った。次に、AP180、CALM及びHip1Rの全長タンパクをGFP融合タンパクとしてCOS7細胞内に発現すると、クラスリンと共局在する小胞状の構造が観察された。中でもHip1Rを含む小胞は、細胞膜直下においてアクチン繊維束に沿って分布することから、エンドサイトーシスとアクチン細胞骨格を結ぶキータンパクである可能性が示唆された。 (2)Epsinファミリーに属する新規タンパクKIAA0171の機能解析を行った。まず、ENTHドメインに対する各イノシトールリン脂質との結合アッセイを行ったところ、PI(4,5)P2に最も強く結合した。GFP融合タンパクをCOS7細胞内に発現したところ、その細胞内局在はクラスリン、およびTGN輸送に関与するアダプタータンパク、AP-1と一致し、その一部はMVB (multi-vesicular body)構造の周縁部に沿って局在することも観察された。次に、さまざまな変異型コンストラクトをGFP融合タンパクとしてCOS7細胞内に発現し、その細胞内局在を検討した。ENTHドメインを欠損すると、KIAA0171のTGN周辺への局在は観察されず、細胞質中に分散する小胞状の局在を示した。脂質結合に必須の67番ArgをAlaに置換した変異体も同様の異常な局在パターンを示した。逆に、ENTHドメインのアミノ末端にミリスチン酸化シグナルを付加した膜結合型変異体ではTGN周辺への集積が促進された。さらに驚くべきことには、ENTHドメインのみをGFP融合タンパクとして発現させると単独でTGNに局在できることが観察され、その局在は67番Arg変異型ENTHドメインでは観察されなかった。

  • イノシトールリン脂質を介したエンドサイトーシス制御機構の解明
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 東京大学, 2001 - 2002
    昨年度の本研究において明らかにした、新規epsinファミリーに属するKIAA0171のさらに詳細な機能解析を行った。 KIAA0171の細胞内局在は、クラスリンだけでなく、トランスゴルジ網(TGN)輸送に関与するアダプタータンパク、AP-1と一致した。また、その一部はエンドソームの融合によって生じるMVB(multi-vesicular body)構造の周縁部に沿って局在することが観察された。実際、in vitroでのpull-down assay及びoverlay assayにより、KIAA0171は一次構造中央部においてクラスリン重鎖、及びγ-adaptinと結合することが明らかとなった。さらに詳細な部分コンストラクトを作製し、検討したところ、これらの結合はそれぞれ、(1)KIAA0171の「SGDLVDLSGDLVDLGFVG」配列とクラスリン重鎖末端ドメイン、及び(2)KIAA0171の「GNGDFGDWSA」配列とγ-adaptinのearドメインとの相互作用によるものであることが明らかとなった。 次に、KIAA0171の細胞内局在とENTHドメインの関係を明らかにするべく、さまざまな変異型コンストラクトをGFP融合タンパクとしてCOS7細胞内に発現し、その細胞内局在を検討した。ENTHドメインを欠損するとKIAA0171のTGN周辺への局在が観察されないことは昨年度に明らかにしていたが、脂質結合に必須の67番ArgをAlaに置換した変異体も同様に、細胞質中に分散する異常な局在パターンを示した。驚くべきことに、ENTHドメインのみをGFP融合タンパクとして発現させると単独でTGNに局在できることが観察され、その局在は67番Arg変異型ENTHドメインでは観察されなかった。

  • Dynamic reorganization of cytoskeletion by WASP family proteins
    TAKENAWA Tadaomi, ITOH Toshiki, FUKAMI Kiyoko
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A), Grant-in-Aid for Scientific Research (A), The University of Tokyo, 2000 - 2002
    It is already well known that a variety of cells rearrange cytoskeleton, prepare for cell division, and stimulate motility and migration in response to various stimuli. The directed migration of cells is one of fundamental phenomena of life, including migration toward inflammatory sites, and invasion and metastasis of cancer cells. We found WASP and WAVE proteins which are related to cytoskeleton reorganization and cell migration. All these proteins have VCA regions at C-terminal area in which V region binds actin and CA region binds Arp2/3 complex. As a result, these proteins nucleate actin filaments and enhance actin polymerization. On the other hand, at N-terminal area, there are regions to which regulatory molecules bind. N-WASP binds several molecules such as WIP, WISH, Cdc42 and PIP2, and WAVE binds IRSp53, followed by the exposure of VCA region of these proteins. Consequently, these proteins bind to Arp2/3 complex and polymerize actin filaments. Finally, N-WASP which is located downstream of Cdc42 induces filopodia formation. WAVE which is located downstream of Rac induces lamellipodia formation. These proteins are present at the leading edge of moving cells and generate driving force.

  • ホスファチジルイノシトール4リン酸5キナーゼの活性制御機構の解析
    伊藤 俊樹
    日本学術振興会, 科学研究費助成事業 特別研究員奨励費, 特別研究員奨励費, 東京大学, 1998 - 1998

TOP