Research activity information

• Sep. 2016 日本生化学会, 日本生化学会奨励賞, 生体膜変形タンパク質による細胞膜の張力を介したアクチン重合制御機構

  Tsujita Kazuya

  Japan society

• Exploring membrane mechanics: The role of membrane-cortex attachment in cell dynamics

  Toshiki Itoh, Kazuya Tsujita

  Elsevier BV, Apr. 2023, Current Opinion in Cell Biology, 81, 102173 - 102173

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Exploring membrane mechanics: The role of membrane-cortex attachment in cell dynamics.

  Toshiki Itoh, Kazuya Tsujita

  The role of plasma membrane (PM) tension in cell dynamics has gained increasing interest in recent years to understand the mechanism by which individual cells regulate their dynamic behavior. Membrane-to-cortex attachment (MCA) is a component of apparent PM tension, and its assembly and disassembly determine the direction of cell motility, controlling the driving forces of migration. There is also evidence that membrane tension plays a role in malignant cancer cell metastasis and stem cell differentiation. Here, we review recent important discoveries that explore the role of membrane tension in the regulation of diverse cellular processes, and discuss the mechanisms of cell dynamics regulated by this physical parameter.

  Apr. 2023, Current opinion in cell biology, 81, 102173 - 102173, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Mechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins.

  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

  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.

  May 2022, Nature communications, 13(1) (1), 2594 - 2594, English, International magazine

  [Refereed]

  Scientific journal


• Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics.

  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

  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.

  May 2022, Nature communications, 13(1) (1), 2347 - 2347, English, International magazine

  [Refereed]

  Scientific journal


• Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly.

  Kazuya Tsujita, Reiko Satow, Shinobu Asada, Yoshikazu Nakamura, Luis Arnes, Keisuke Sako, Yasuyuki Fujita, Kiyoko Fukami, Toshiki Itoh

  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.

  Corresponding, Oct. 2021, Nature communications, 12(1) (1), 5930 - 5930, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• PTEN is required for the migration and invasion of Ras‐transformed MDCK cells

  Lu Yan, Kazuya Tsujita, Yasuyuki Fujita, Toshiki Itoh

  The balance between phosphoinositides distributed at specific sites in the plasma membrane causes polarized actin polymerization. Oncogenic transformations affect this balance by regulating phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN), causing metastatic behavior in cancer cells. Here, we show that the PTEN tumor suppressor gene is required for epithelial cancer cell invasion. Loss of PTEN in Ras-transformed MDCK cells suppressed their migratory phenotype in collagen gel and invasion through Matrigel. Rescue experiments showed a requirement for the C2 domain-mediated membrane recruitment of PTEN, which is typically observed at the rear side of invading cancer cells. These findings support the role of PTEN in suppression of unwanted leading edges necessary for efficient migration of epithelial cancer cells.

  Wiley, May 2021, FEBS Letters, 595(9) (9), 1303 - 1312, English, International magazine

  [Refereed]

  Scientific journal


• Non-cell-autonomous migration of RasV12-transformed cells towards the basal side of surrounding normal cells

  Imen Jebri, Kazuya Tsujita, Yasuyuki Fujita, Toshiki Itoh

  Oncogenic transformation enables cells to behave differently from their neighboring normal cells. Both cancer and normal cells recognize each other, often promoting the extrusion of the former from the epithelial cell layer. Here, we show that RasV12-transformed normal rat kidney 52E (NRK-52E) cells are extruded towards the basal side of the surrounding normal cells, which is concomitant with enhanced motility. The active migration of the basally extruded RasV12 cells is observed when surrounded by normal cells, indicating a non-cell-autonomous mechanism. Furthermore, specific inhibitor treatment and knockdown experiments elucidate the roles of PI3K and myosin IIA in the basal extrusion of Ras cells. Our findings reveal a new aspect of cancer cell invasion mediated by functional interactions with surrounding non-transformed cells.

  Elsevier BV, Mar. 2021, Biochemical and Biophysical Research Communications, 543, 15 - 22, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor.

  Hasegawa J, Imen J, Yamamoto H, Tsujita K, Tokuda E, Shibata H, Maki M, Itoh T

  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 C-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.

  Sep. 2019, Journal of Cell Science, 132(19) (19), English, International magazine

  [Refereed]

  Scientific journal


• An influenza-derived membrane tension-modulating peptide regulates cell movement and morphology via actin remodeling.

  Masuda T, Baba K, Nomura T, Tsujita K, Murayama T, Itoh T, Takatani-Nakase T, Sokabe M, Inagaki N, Futaki S

  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.

  2019, Communications Biology, 2, 243 - 243, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Phosphoinositides in the regulation of actin cortex and cell migration.

  Kazuya Tsujita, Toshiki Itoh

  In order for the cell to function well within a multicellular system, the mechanical properties of the plasma membrane need to meet two different requirements: cell shape maintenance and rearrangement. To achieve these goals, phosphoinositides play key roles in the regulation of the cortical actin cytoskeleton. PI(4,5)P₂is the most abundant phosphoinositide species in the plasma membrane. It maintains cell shape by linking the actin cortex to the membrane via interactions with Ezrin/Radixin/Moesin (ERM) proteins and class I myosins. Although the role of D3-phosphoinositides, such as PI(3,4,5)P₃, in actin-driven cell migration has been a subject of controversy, it becomes evident that the dynamic turnover of the phosphoinositide by the action of metabolizing enzymes, such as 5-phosphatases, is necessary. Recent studies have revealed an important role of PI(3,4)P₂in podosome/invadopodia formation, shedding new light on the actin-based organization of membrane structures regulated by phosphoinositide signaling. This article is part of a Special Issue entitled Phosphoinositides.

  Jun. 2015, Biochimica et biophysica acta, 1851(6) (6), 824 - 31, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Feedback regulation between plasma membrane tension and membrane-bending proteins organizes cell polarity during leading edge formation

  Kazuya Tsujita, Tadaomi Takenawa, Toshiki Itoh

  Jun. 2015, Nature Cell Biology, 17(6) (6), 749 - +, English, International magazine

  [Refereed]

  Scientific journal


• Antagonistic regulation of F-BAR protein assemblies controls actin polymerization during podosome formation

  Kazuya Tsujita, Akihiro Kondo, Shusaku Kurisu, Junya Hasegawa, Toshiki Itoh, Tadaomi Takenawa

  May 2013, Journal of Cell Science, 126(10) (10), 2267 - 2278, English, International magazine

  [Refereed]

  Scientific journal


• Physicochemical Analysis from Real-Time Imaging of Liposome Tubulation Reveals the Characteristics of Individual F-BAR Domain Proteins

  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, English, International magazine

  [Refereed]

  Scientific journal


• ARAP1 regulates the ring size of circular dorsal ruffles through Arf1 and Arf5

  Junya Hasegawa, Kazuya Tsujita, Tadaomi Takenawa, Toshiki Itoh

  Jul. 2012, Molecular Biology of the Cell, 23(13) (13), 2481 - 2489, English, International magazine

  [Refereed]

  Scientific journal


• Characterization of the EFC/F-BAR domain protein, FCHO2

  Akiyoshi Uezu, Kazuaki Umeda, Kazuya Tsujita, Shiro Suetsugu, Tadaomi Takenawa, Hiroyuki Nakanishi

  Aug. 2011, Genes to Cells, 16(8) (8), 868 - 878, English, International magazine

  [Refereed]

  Scientific journal


• SH3YL1 regulates dorsal ruffle formation by a novel phosphoinositide-binding domain

  Junya Hasegawa, Emi Tokuda, Takeshi Tenno, Kazuya Tsujita, Haruko Sawai, Hidekazu Hiroaki, Tadaomi Takenawa, Toshiki Itoh

  May 2011, Journal of Cell Biology, 193(5) (5), 901 - 916, English, International magazine

  [Refereed]

  Scientific journal


• Nebulin and N-WASP Cooperate to Cause IGF-1-Induced Sarcomeric Actin Filament Formation

  Kazunori Takano, Haruko Watanabe-Takano, Shiro Suetsugu, Souichi Kurita, Kazuya Tsujita, Sumiko Kimura, Takashi Karatsu, Tadaomi Takenawa, Takeshi Endo

  Dec. 2010, Science, 330(6010) (6010), 1536 - 1540, English, International magazine

  [Refereed]

  Scientific journal


• Proteome of Acidic Phospholipid-binding Proteins SPATIAL AND TEMPORAL REGULATION OF CORONIN 1A BY PHOSPHOINOSITIDES

  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, English, International magazine

  [Refereed]

  Scientific journal


• The Tyrosine Kinase Fer Is a Downstream Target of the PLD-PA Pathway that Regulates Cell Migration

  Toshiki Itoh, Junya Hasegawa, Kazuya Tsujita, Yasunori Kanaho, Tadaomi Takenawa

  Sep. 2009, Science Signaling, 2(87) (87), ra52, English, International magazine

  [Refereed]

  Scientific journal


• SGIP1alpha is an endocytic protein that directly interacts with phospholipids and Eps15.

  Uezu A, Horiuchi A, Kanda K, Kikuchi N, Umeda K, Tsujita K, Suetsugu S, Araki N, Yamamoto H, Takenawa T, Nakanishi H

  SGIP1 has been shown to be an endophilin-interacting protein that regulates energy balance, but its function is not fully understood. Here, we identified its splicing variant of SGIP1 and named it SGIP1alpha. SGIP1alpha bound to phosphatidylserine and phosphoinositides and deformed the plasma membrane and liposomes into narrow tubules, suggesting the involvement in vesicle formation during endocytosis. SGIP1alpha furthermore bound to Eps15, an important adaptor protein of clathrin-mediated endocytic machinery. SGIP1alpha was colocalized with Eps15 and the AP-2 complex. Upon epidermal growth factor (EGF) stimulation, SGIP1alpha was colocalized with EGF at the plasma membrane, indicating the localization of SGIP1alpha at clathrin-coated pits/vesicles. SGIP1alpha overexpression reduced transferrin and EGF endocytosis. SGIP1alpha knockdown reduced transferrin endocytosis but not EGF endocytosis; this difference may be due to the presence of redundant pathways in EGF endocytosis. These results suggest that SGIP1alpha plays an essential role in clathrin-mediated endocytosis by interacting with phospholipids and Eps15.

  Sep. 2009, Journal of Biological Chemistry, 282(36) (36), 26481 - 9, English, International magazine

  [Refereed]

  Scientific journal


• Curved EFC/F-BAR-domain dimers are joined end to end into a filament for membrane invagination in endocytosis

  Atsushi Shimada, Hideaki Niwa, Kazuya Tsujita, Shiro Suetsugu, Koji Nitta, Kyoko Hanawa-Suetsugu, Ryogo Akasaka, Yuri Nishino, Mitsutoshi Toyama, Lirong Chen, Zhi-Jie Liu, Bi-Cheng Wang, Masaki Yamamoto, Takaho Terada, Atsuo Miyazawa, Akiko Tanaka, Sumio Sugano, Mikako Shirouzu, Kuniaki Nagayama, Tadaomi Takenawa, Shigeyuki Yokoyama

  May 2007, Cell, 129(4) (4), 761 - 772, English, International magazine

  [Refereed]

  Scientific journal


• Application of phosphoinositide-binding domains for the detection and quantification of specific phosphoinositides

  Masahiro Furutani, Kazuya Tsujita, Toshiki Itoh, Takeshi Ijuin, Tadaomi Takenawa

  Aug. 2006, ANALYTICAL BIOCHEMISTRY, 355(1) (1), 8 - 18, English, International magazine

  [Refereed]

  Scientific journal


• Thin layer chromatography-blotting, a novel method for the detection of phosphoinositides

  Masahiro Furutani, Toshiki Itoh, Takeshi Ijuin, Kazuya Tsujita, Tadaomi Takenawa

  Apr. 2006, Journal of Biochemistry, 139(4) (4), 663 - 670, English, International magazine

  [Refereed]

  Scientific journal


• Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis

  K Tsujita, S Suetsugu, N Sasaki, M Furutani, T Oikawa, T Takenawa

  Jan. 2006, Journal of Cell Biology, 172(2) (2), 269 - 279, English, International magazine

  [Refereed]

  Scientific journal


• Myotubularin regulates the function of the late endosome through the GRAM domain-phosphatidylinositol 3,5-bisphosphate interaction

  K Tsujita, T Itoh, T Ijuin, A Yamamoto, A Shisheva, J Laporte, T Takenawa

  Apr. 2004, Journal of Biological Chemistry, 279(14) (14), 13817 - 13824, English, International magazine

  [Refereed]

  Scientific journal

• Regulation of Cell Membrane Tension by Membrane Curvature-Inducing Proteins

  辻田和也, 伊藤俊樹

  2021, 日本細胞生物学会大会(Web), 73rd


• 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

  2021, 日本生化学会大会(Web), 94th


• 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

  2020, 日本薬学会年会要旨集(CD-ROM), 140th


• DA-Rafはリン脂質とRasの両方に結合することでRas-ERKカスケードを抑制する

  高野 和儀, 辻田 和也, 菅野 英美里, 菅波 晃子, 遠藤 剛

  (一社)日本細胞生物学会, May 2017, 日本細胞生物学会大会講演要旨集, 69回, 134 - 134, Japanese


• 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


• SGIP1αによる膜輸送の制御

  堀内 綾香, 上江洲 章吉, 神田 絋介, 辻田 和也, 末次 志郎, 荒木 令江, 清末 優子, 山本 秀幸, 竹縄 忠臣, 中西 宏之

  (公社)日本薬理学会, Feb. 2007, 日本薬理学雑誌, 129(2) (2), 42P - 42P, Japanese

• 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


• Role of plasma membrane tension in cell migration and invasion

  Tsujita Kazuya

  第55回生物物理学会シンポジウム, Sep. 2017, English, 日本生物物理学会, 熊本, Domestic conference

  [Invited]

  Invited oral presentation


• 癌細胞の浸潤・転移を司る細胞膜の張力を介したシグナル伝達機構の解明

  Tsujita Kazuya

  メカノバイオロジー機構の解明による革新的医療機器及び医療技術の創出 平成27年度キックオフミーティング, Feb. 2016, Japanese, AMED, 東京, Domestic conference

  [Invited]

  Nominated symposium


• 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


• 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


• Feedback regulation between plasma membrane tension and membrane-bending proteins in cell migration

  Tsujita Kazuya

  The26th CDB Meeting, Sep. 2015, English, 理研CDB, 神戸, Domestic conference

  Public symposium


• 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


• 細胞運動における細胞膜の張力と膜変形タンパク質によるフィードバック制御機構

  Tsujita Kazuya

  大阪大学微生物病研究所セミナー, Jun. 2015, Japanese, 大阪大学, 大阪, Domestic conference

  [Invited]

  Invited oral 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


• 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


• 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

• THE JAPANESE CONFERENCE ON THE BIOCHEMISTRY OF LIPIDS


• JAPAN SOCIETY FOR CELL BIOLOGY


• THE JAPANESE BIOCHEMICAL SOCIETY

• がん細胞の細胞膜張力を標的とした化合物の探索と治療法への応用

  辻田 和也

  日本学術振興会, 科学研究費助成事業 挑戦的研究(萌芽), 挑戦的研究(萌芽), 神戸大学, 30 Jun. 2022 - 31 Mar. 2024


• Mechanism of Cell Membrane Tension Homeostasis by Membrane Tension Sensor Proteins

  Tsujita Kazuya

  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

  This study focused on BAR proteins that induce and sense membrane curvature to elucidate the molecular mechanisms by which plasma membrane tension homeostasis is maintained in epithelial cells. Using a combination of optical tweezers and gene knockdown experiments, we identified a BAR protein X that is required for homeostasis of plasma membrane tension. We found that, X, which has a GAP domain for Rac, recruit to the membrane by sensing decreased membrane tension, where it inactive Rac, which in turn activates its competitor, RhoA. This RhoA activation seems to lead to increased membrane tension by increasing membrane-cortex attachment. These results suggest that a feedback regulation between plasma membrane tension and BAR protein X plays an important role in tensional homeostasis of the plasma membrane.


• 細胞膜の張力を可視化するプローブの開発

  辻田 和也

  学術研究助成基金助成金／挑戦的萌芽研究, Apr. 2016 - Mar. 2018, Principal investigator

  Competitive research funding


• 【AMED】癌細胞の浸潤・転移を司る細胞膜の張力を介したシグナル伝達機構の解明

  辻田 和也

  国立研究開発法人日本医療研究開発機構, 革新的先端研究開発支援事業ソロタイプ「メカノバイオロジー機構の解明による革新的医療機器及び医療技術の創出」」研究開発領域, 2017, Principal investigator

  Competitive research funding


• Regulation of cell dynamism by phosphoinositides

  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), 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.


• 細胞膜の張力を介したアクチン重合制御機構の解明

  辻田 和也

  学術研究助成基金助成金／基盤研究(C), Apr. 2013 - Mar. 2016, Principal investigator

  Competitive research funding


• Molecular mechanism of endocytosis by a novel membrane-bending domain

  ITOH TOSHIKI, TSUJITA Kazuya

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2012 - 31 Mar. 2015

  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.


• アクチンカップ形成におけるＥＦＣ／Ｆ－ＢＡＲタンパク質であるＦＢＰ１７の役割

  辻田 和也

  学術研究助成基金助成金／若手研究(B), 2011, Principal investigator

  Competitive research funding


• 自己炎症性疾患の原因タンパク質であるＰＳＴＰＩＰｓの細胞運動における役割

  辻田 和也

  科学研究費補助金／若手研究(B), 2008, Principal investigator

  Competitive research funding