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SAKISAKA Toshiaki
Graduate School of Medicine / Faculty of Medical Sciences
Professor

Researcher basic information

■ Research Areas
  • Life sciences / Medical biochemistry

Research activity information

■ Award
  • Oct. 2008 日本生化学会, 日本生化学会奨励賞, 小胞輸送による神経軸索形成機構
    Sakisaka Toshiaki

■ Paper
  • Hiroaki Kajiho, Toshiaki Sakisaka
    Autophagy is classified as non-selective or selective depending on the types of degrading substrates. Endoplasmic reticulum (ER)-phagy is a form of selective autophagy for transporting the ER-resident proteins to autolysosomes. FAM134B, a member of the family with sequence similarity 134, is a well-known ER-phagy receptor. Dysfunction of FAM134B results in several diseases including viral infection, inflammation, neurodegenerative disorder and cancer, indicating that FAM134B has crucial roles in various kinds of intracellular functions. However, how FAM134B-mediated ER-phagy regulates intracellular functions is not well understood. In this study, we found that FAM134B knockdown in mammalian cells accelerated cell proliferation. FAM134B knockdown increased the protein amount of STIM1, an ER Ca2+ sensor protein mediating the store-operated Ca2+ entry (SOCE) involved in G1 to S phase transition. FAM134B bound to STIM1 through its C-terminal cytosolic region. FAM134B knockdown reduced transport of STIM1 from the ER to autolysosomes. Finally, FAM134B knockdown accelerated G1 to S phase transition. These results suggest that FAM134B is involved in cell proliferation possibly through degradation of STIM1 via ER-phagy.
    Last, Aug. 2024, The Journal of Biological Chemistry, 300(9) (9), 107674 - 107674, English, International magazine
    [Refereed]
    Scientific journal

  • Saihas Suhda, Yasunori Yamamoto, Sindhu Wisesa, Risa Sada, Toshiaki Sakisaka
    The reticular network of the endoplasmic reticulum (ER) is formed by connecting ER tubules through three-way junctions and undergoes constant remodeling through formation and loss of the three-way junctions. Transmembrane and coiled-coil domain family 3 (TMCC3), an ER membrane protein localizing at three-way junctions, has been shown to positively regulate formation of the reticular ER network. However, elements that negatively regulate TMCC3 localization have not been characterized. In this study, we report that 14-3-3γ, a phospho-serine/phospho-threonine-binding protein involved in various signal transduction pathways, is a negative regulator of TMCC3. We demonstrate that overexpression of 14-3-3γ reduced localization of TMCC3 to three-way junctions and decreased the number of three-way junctions. TMCC3 bound to 14-3-3γ through the N terminus and had deduced 14-3-3 binding motifs. Additionally, we determined that a TMCC3 mutant substituting alanine for serine to be phosphorylated in the binding motif reduced binding to 14-3-3γ. The TMCC3 mutant was more prone than wildtype TMCC3 to localize at three-way junctions in the cells overexpressing 14-3-3γ. Furthermore, the TMCC3 mutant rescued the ER sheet expansion caused by TMCC3 knockdown less than wild-type TMCC3. Taken together, these results indicate that 14-3-3γ binding negatively regulates localization of TMCC3 to the three-way junctions for the proper reticular ER network, implying that the negative regulation of TMCC3 by 14-3-3γ would underlie remodeling of the reticular network of the ER.
    Feb. 2023, The Journal of Biological Chemistry, 299(2) (2), 102813 - 102813, English, International magazine
    [Refereed]
    Scientific journal

  • Putri Chynthia Anggrandariyanny, Hiroaki Kajiho, Yasunori Yamamoto, Toshiaki Sakisaka
    Endoplasmic reticulum (ER) tubules are interconnected by three-way junctions, resulting in the formation of a tubular ER network. Lunapark (Lnp) localizes to and stabilizes the three-way junctions. The N-terminal cytoplasmic domain in Lnp has a ubiquitin ligase activity. However, the molecular mechanism of how the ubiquitin ligase activity of Lnp is involved in the formation of the tubular ER network remains unknown. In this study, we examined whether the ER membrane proteins responsible for the formation of the tubular ER network are ubiquitinated by Lnp. We found that atlastin-2 (ATL2), an isoform of the ATL family mediating the generation of the three-way junctions by connecting the ER tubules, is a novel substrate for ubiquitination by Lnp. The localization of Lnp at the three-way junctions is important for ubiquitination of ATL2. Lysine 56, 57, 282 and 302 are the potential ubiquitination sites by Lnp. Silencing ATL2 decreased the number of the three-way junctions, and the expression of the ATL2 mutant in which the lysine residues are substituted with arginine failed to rescue the decrease of the three-way junctions in the ATL2 knocked-down cells. These results suggest that Lnp ubiquitinates ATL2 at the three-way junctions for the proper tubular ER network formation.
    Sep. 2022, Journal of biochemistry, 172(4) (4), 245 - 257, English, International magazine
    [Refereed]
    Scientific journal

  • Yasunori Uchida, Yasunori Yamamoto, Toshiaki Sakisaka
    Elsevier BV, Jan. 2021, The Journal of Biological Chemistry, 100310 - 100310, English
    [Refereed]
    Scientific journal

  • Wisesa S, Yamamoto Y, Sakisaka T
    Oct. 2019, Biochemical Journal
    [Refereed]

  • Kajiho H, Yamamoto Y, Sakisaka T
    Sep. 2019, Scientific Reports, 9(1) (1), 13152
    [Refereed]


  • The number of the C-terminal transmembrane domains has the potency to specify subcellular localization of Sec22c
    Yamamoto Yasunori, YurugiC, Sakisaka Toshiaki
    May 2017, Biochem Biophys Res Commun, 487(2) (2), 388 - 395, English
    [Refereed]
    Scientific journal

  • Kif14 overexpression accelerates murine retinoblastoma development
    OHare M, Shadmand M, Sulaiman RS, Sishtla K, Sakisaka Toshiaki, Corson TW
    Oct. 2016, Int J Cancer, 139(8) (8), 1752 - 8, English
    [Refereed]
    Scientific journal

  • The emerging role of calcium-modulating cyclophilin ligand in posttranslational insertion of tail-anchored proteins into the endoplasmic reticulum membrane
    Yamamoto Yasunori, Sakisaka Toshiaki
    Jun. 2015, J Biochem, 157(6) (6), 419 - 29, English
    [Refereed]
    Scientific journal

  • Crystal structure of afadin PDZ domain-nectin-3 complex shows the structural plasticity of the ligand-binding site
    Fujiwara Y, Goda N, Tamashiro T, Narita H, Satomura K, Tenno T, Nakagawa A, Oda M, Suzuki M, Sakisaka Toshiaki, Takai Yoshimi, Hiroaki H
    Mar. 2015, Protein Sci, 24(3) (3), 376 - 85, English
    [Refereed]
    Scientific journal

  • Identification and Characterization of TMEM33 as a Reticulon-binding Protein
    Urade T, Yamamoto Yasunori, Zhang X, Ku Yonson, Sakisaka Toshiaki
    Nov. 2014, Kobe J Med Sci, 60(3) (3), E57 - 65, English
    [Refereed]
    Scientific journal

  • VAP-B Binds to Rab3GAP1 at the ER: Its Implication in Nuclear Envelope Formation through the ER-Golgi Intermediate Compartment
    Hantan D, Yamamoto Yasunori, Sakisaka Toshiaki
    Oct. 2014, Kobe J Med Sci, 60(3) (3), E48 - 56, English
    [Refereed]
    Scientific journal

  • Cytoarchitecture of the olfactory bulb in the laggard mutant mouse
    Yunus J, Setsu T, Kikkawa S, Sakisaka Toshiaki, Terashima Toshio
    Sep. 2014, Neuroscience, 275, 259 - 71, English
    [Refereed]
    Scientific journal

  • Arl6IP1 has the ability to shape the mammalian ER membrane in a reticulon-like fashion
    Yamamoto Yasunori, Yoshida A, Miyazaki N, Iwasaki K, Sakisaka Toshiaki
    Feb. 2014, Biochemical Journal, 458(1) (1), 69 - 79, English
    [Refereed]
    Scientific journal

  • Kif14 mutation causes severe brain malformation and hypomyelination
    Fujikura K, Setsu T, Tanigaki K, Abe T, Kiyonari H, Terashima T, Sakisaka T
    Jan. 2013, PLoS One, 8(1) (1), e53490, English
    [Refereed]
    Scientific journal

  • Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells
    Yamamoto Yasunori, Sakisaka Toshiaki
    Nov. 2012, Molecular Cell, 48(3) (3), 387 - 97, English
    [Refereed]
    Scientific journal

  • Crystal Structure of the cis-Dimer of Nectin-1: implications for the architecture of cell-cell junctions
    Narita H, Yamamoto Y, ual contribution, Suzuki M, Miyazaki N, Yoshida A, Kawai K, Iwasaki K, Nakagawa A, Takai Y, Sakisaka T
    Apr. 2011, The Journal of Biological Chemistry, Vol. 286, No. 14, pp. 12659-69, English
    [Refereed]
    Scientific journal

  • Refolding, crystallization and preliminary X-ray crystallographic study of the whole extracellular regions of nectins
    Narita H, Nakagawa A, Yamamoto Y, Sakisaka T, Takai Y, Suzuki M
    Mar. 2011, Acta crystallographica. Section F, Structural biology and crystallization communications, Vol. 67, No. Pt 3, pp. 344-8, English
    [Refereed]
    Scientific journal

  • Dual regulation of RA-RhoGAP activity by phosphatidic acid and Rap1 during neurite outgrowth
    Kurooka T, Yamamoto Y, Takai Y, Sakisaka T
    Feb. 2011, The Journal of Biological Chemistry, Vol. 286, No. 8, pp. 6832-43, English
    [Refereed]
    Scientific journal

  • Tomosyn inhibits synaptotagmin-1-mediated step of Ca2 -dependent neurotransmitter release through its N-terminal WD40 repeats
    Yamamoto Y, Mochida S, Miyazaki N, Kawai K, Fujikura K, Kurooka T, Iwasaki K, Sakisaka T
    Dec. 2010, The Journal of Biological Chemistry, Vol. 285, No. 52, pp. 40943-55, English
    [Refereed]
    Scientific journal

  • The tail domain of tomosyn controls membrane fusion through tomosyn displacement by VAMP2
    Yamamoto Y, Fujikura K, Sakaue M, Okimura K, Kobayashi Y, Nakamura T, Sakisaka T
    Aug. 2010, Biochemical and Biophysical Research Communications, Vol. 399, No. 1, pp. 24-30, English
    [Refereed]
    Scientific journal

  • Involvement of afadin in the formation and remodeling of synapses in the hippocampus
    Majima T, Ogita H, Yamada T, Amano H, Togashi H, Sakisaka T, Tanaka-Okamoto M, Ishizaki H, Miyoshi J, Takai Y
    Aug. 2009, Biochemical and Biophysical Research Communications, Vol. 385, No. 4, pp. 539-44, English
    [Refereed]
    Scientific journal

  • Reciprocal intramolecular interactions of tomosyn control its inhibitory activity on SNARE complex formation
    Yamamoto Y, Mochida S, Kurooka T, Sakisaka T
    May 2009, The Journal of Biological Chemistry, Vol. 284, No. 18, pp. 12480-12, English
    [Refereed]
    Scientific journal

  • Cell adhesion molecules in the central nervous system
    Togashi Hideru, Sakisaka Toshiaki, Takai Yoshimi
    Jan. 2009, Cell Adh Migr, 3(1) (1), 29 - 35, English
    [Refereed]
    Scientific journal

  • Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release
    Sakisaka T, Yamamoto Y, ual contribution, Mochida S, Nakamura M, Nishikawa K, Ishizaki H, Okamoto-Tanaka M, Miyoshi J, Fujiyoshi Y, Manabe T, Takai Y
    Lead, Oct. 2008, The Journal of Cell Biology, Vol. 183, No. 2, pp. 323-37, English
    [Refereed]
    Scientific journal

■ MISC
  • 【テイルアンカー型タンパク質の細胞内輸送と膜挿入機構:現代生物学に残された謎の一つがいま解かれる】 テイルアンカー型タンパク質のトランスロコン非依存的な小胞体輸送・膜挿入機構
    Yamamoto Yasunori, Sakisaka Toshiaki
    Jul. 2013, 細胞工学, 32(8号) (8号), 845 - 850, Japanese
    [Invited]
    Introduction commerce magazine

  • 【SNARE複合体-膜融合の機構】 トモシンによるSNARE複合体の制御機構
    Yamamoto Yasunori, Sakisaka Toshiaki
    Jun. 2010, 生体の科学, 61巻, 3号, pp. 233-241, Japanese
    Introduction scientific journal

  • 全く新しいトモシンによる小胞融合の制御機構
    Sakisaka Toshiaki
    Oct. 2009, 生化学, 81巻, 10号, pp. 863-872, Japanese
    Introduction scientific journal

  • 【融合発展する構造生物学とケミカルバイオロジーの最前線】 ターゲットタンパク研究プログラムの成果 細胞接着装置構成蛋白質の構造生物学的研究 Lglファミリー分子トモシンによる小胞融合の制御機構
    Yamamoto Yasunori, Sakisaka Toshiaki
    Sep. 2009, 蛋白質・核酸・酵素, 54巻, 12号, pp. 1647-1653, Japanese
    Introduction scientific journal

  • 【メンブレントラフィックの奔流 分子から細胞、そして個体へ】 メンブレントラフィックと高次機能 メンブレントラフィックと神経系 軸索形成における小胞輸送の役割
    Yamamoto Yasunori, Sakisaka Toshiaki
    Dec. 2008, 蛋白質・核酸・酵素, 53巻, 16号, pp. 2207-2213, Japanese
    Introduction scientific journal

  • A cell-free assay for endocytosis of E-cadherin
    Sakisaka Toshiaki
    2008, Methods in molecular biology (Clifton, NJ), Vol. 440, No. , pp. 77-87, English
    [Refereed]
    Introduction scientific journal

  • The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors
    Sakisaka Toshiaki
    Oct. 2007, Current Opinion In Cell Biology, Vol. 19, No. 5, pp. 593-602, English
    Introduction scientific journal

■ Books And Other Publications
  • メンブレントラフィック 膜・小胞による細胞内輸送ネットワーク / 神経伝達物質放出を支えるメンブレントラフィック
    Yamamoto Yasunori, Sakisaka Toshiaki
    Others, 化学同人, Jul. 2016, Japanese
    Scholarly book

  • Presynaptic Terminals / Roles of tomosyn in neurotransmitter release
    Yamamoto Yasunori, Toshiaki Sakiaska, Sakisaka Toshiaki
    Others, Springer, 2015, English
    Scholarly book

  • 細胞接着装置構成蛋白質の構造生物学的研究--Lglファミリー分子トモシンによる小胞融合の制御機構 (融合発展する構造生物学とケミカルバイオロジーの最前線) -- (ターゲットタンパク研究プログラムの成果)
    山本泰憲, SAKISAKA TOSHIAKI
    Others, 蛋白質核酸酵素, Sep. 2009, Japanese
    Others

  • メンブレントラフィックと神経系 軸索形成における小胞輸送の役割 (メンブレントラフィックの奔流--分子から細胞,そして個体へ) -- (メンブレントラフィックと高次機能)
    山本泰憲, SAKISAKA TOSHIAKI
    Others, 蛋白質核酸酵素, Dec. 2008, Japanese
    Others

■ Lectures, oral presentations, etc.
  • 小胞体膜タンパク質TMCC3による小胞体の網目状ネットワークの形成調節機構
    山本 泰憲, Sindhu Wisesa, 匂坂 敏朗
    第94回日本生化学会大会, Nov. 2021, 日本生化学会

  • ユビキチンリガーゼ活性による小胞体網目構造の新しい形態調節機構
    梶保 博昭, 山本 泰憲, 匂坂 敏朗
    第93回日本生化学会大会, Sep. 2020, 日本生化学会

  • 小胞体の網目構造を調節する因子の多量体化機構
    KAJIHO HIROAKI, YAMAMOTO YASUNORI, 姜 山, SAKISAKA TOSHIAKI
    第65回日本生化学会 近畿支部例会, May 2018, Japanese, 日本生化学会, 西宮, Domestic conference
    Oral presentation

  • ユビキチンリガーゼ活性による小胞体の新しい形態調節機構
    Kajiho Hiroaki, Yamamoto Yasunori, Sakisaka Toshiaki
    ConBio2017, Dec. 2017, Japanese, 日本分子生物学会、日本生化学会, 神戸, Domestic conference
    Oral presentation

  • ペルオキシソーム形成因子による小胞体膜変形タンパク質reticulonの翻訳後膜挿入機構
    Yamamoto Yasunori, Sakisaka Toshiaki
    ConBio2017, Dec. 2017, Japanese, 日本分子生物学会、日本生化学会, 神戸, Domestic conference
    Poster presentation

  • 小胞輸送調節タンパク質Sec22CはC末膜貫通領域の数により細胞内局在を制御する
    Yamamoto Yasunori, 萬木 千聖, Sakisaka Toshiaki
    第64回 日本生化学学会 近畿支部例会, May 2017, Japanese, 日本生化学学会 近畿支部, 大阪, Domestic conference
    Oral presentation

  • 小胞体膜タンパク質による極長鎖脂肪酸合成の制御
    Uchida Yasunori, Yamamoto Yasunori, 出来 宏晃, Sakisaka Toshiaki
    第64回 日本生化学学会 近畿支部例会, May 2017, Japanese, 日本生化学学会 近畿支部, 大阪, Domestic conference
    Oral presentation

  • ユビキチンリガーゼによる小胞体の形態制御機構
    Kajiho Hiroaki, 姜 山, Yamamoto Yasunori, Sakisaka Toshiaki
    第64回 日本生化学学会 近畿支部例会, May 2017, Japanese, 日本生化学学会 近畿支部, 大阪, Domestic conference
    Oral presentation

  • 髄鞘低形成と皮質形成異常を示す新規突然変異マウスlaggard
    Sakisaka Toshiaki, Terashima Toshio
    第121回日本解剖学会総会全国学術集会, Mar. 2016, Japanese, The Japanese Association of Anatomists, 福島県(郡山市), Domestic conference
    [Invited]
    Invited oral presentation

  • Cytoarchitecture of the cerebellum in the laggard mutant mouse.
    ジュナエヂィ ユヌス, 薛富義, Kikkawa Satoshi, Sakisaka Toshiaki, Terashima Toshio
    The 38th Japan Neuroscience Meeting, Jul. 2015, Japanese, The Japan Neuroscience Association, 神戸, Domestic conference
    Poster presentation

  • Cytoarchitecture of the cerebellum in the laggard mutant mouse.
    Junaedy Yunus, Tomiyoshi Setsu, Kikkawa Satoshi, Sakisaka Toshiaki, Terashima Toshio
    第120回日本解剖学会総会, Mar. 2015, English, 日本解剖学会, 神戸市, Domestic conference
    Poster presentation

  • Brain morphology of Kif14 KO mouse and Kif14 Tg rescue mouse
    Terashima Toshio, 薛富義, Junaedy Yunus, Sakisaka Toshiaki
    第90回日本解剖学会近畿支部学術集会, Nov. 2014, Japanese, 日本解剖学会, 大阪, Domestic conference
    Oral presentation

  • Molecular mechanisms underlying ER morphology and posttranslational insertion of membrane proteins into the ER membrane
    Yamamoto Yasunori, Sakisaka Toshiaki
    The 87th Annual Meeting of the Japanese Biochemical Society, Oct. 2014, Japanese, 日本生化学会, 京都, Domestic conference
    [Invited]
    Nominated symposium

  • Identification and Characterization of TMEM33 as a Reticulon-binding Protein
    張 霞, Yamamoto Yasunori, 浦出 剛史, Sakisaka Toshiaki
    The 36th Annual Meeting of The Molecular Biology Society of Japan, Dec. 2013, Japanese, The Molecular Biology Society of Japan, 神戸, Domestic conference
    Poster presentation

  • 髄鞘低形成と小脳性運動失調を呈するlaggardマウスの皮質構築異常
    薛 富義, 藤倉 航平, 崎浜 吉昭, Sakisaka Toshiaki, Terashima Toshio
    第118回日本解剖学会総会, Mar. 2013, Japanese, 日本解剖学会, 高松, Domestic conference
    Poster presentation

  • 高等真核細胞おける尾部アンカー型膜タンパク質の小胞体膜挿入装置の発見
    Yamamoto Yasunori, Sakisaka Toshiaki
    The 85th Annual Meeting of the Japanese Biochemical Society, Dec. 2012, Japanese, The Japanese Biochemical Society, 福岡, Domestic conference
    Oral presentation

  • New mutant mouse characterized with hypomyelination and cerebellar ataxia
    薛 富義, 藤倉 航平, 黒岡 貴生, 崎浜 吉昭, Sakisaka Toshiaki, Terashima Toshio
    第117回日本解剖学会総会全国学術集会, Mar. 2012, Japanese, 日本解剖学会, 西宮, Domestic conference
    Oral presentation

  • Central myelinof the laggard mutant mice based on LM and EM analysis
    Terashima Toshio, 薛 富義, 藤倉 航平, 黒岡 貴生, 崎浜 吉昭, Sakisaka Toshiaki
    第87回日本解剖学会近畿支部学術集会, Dec. 2011, Japanese, 日本解剖学会, 西宮, Domestic conference
    Oral presentation

  • ネクチン3のC末端配列と結合したアファディンPDZドメインの構造解析
    藤原芳江, 合田名都子, 里村香織, 成田宏隆, 中川敦史, Takai Yoshimi, Sakisaka Toshiaki, 鈴木守, 廣明秀一
    平成23年度日本結晶学会年会, Nov. 2011, Japanese, 日本結晶学会, 札幌, Domestic conference
    Poster presentation

  • A new mutant mouse with hypomyelination and cerebellar ataxia
    Terashima Toshio, 藤倉 航平, 黒岡 貴生, Sakisaka Toshiaki
    第34回日本神経科学大会, Sep. 2011, Japanese, 日本神経科学学会, 横浜, Domestic conference
    Poster presentation

  • Involvement of p38, an ER-localized membrane protein, in insertion of tail-anchored proteins into the ER membrane
    Yamamoto Yasunori, Sakisaka Toshiaki
    第84回日本生化学会大会, Sep. 2011, Japanese, 日本生化学会, 京都, Domestic conference
    Oral presentation

  • Structure determination of afadin PDZ domain complexed with nectin-3 C-terminus.
    藤原芳江, 合田(天野, 名都子, 里村香織, 成田宏隆, 中川敦史, Sakisaka Toshiaki, 鈴木守, 廣明秀一
    第33回日本分子生物学会年会 (BMB2010), Dec. 2010, Japanese, 日本分子生物学会, 神戸, Domestic conference
    Poster presentation

  • Positive and negative roles of tomosyn in synaptic vesicle exocytosis.
    Yamamoto Yasunori, 藤倉 航平, 阪上 海央, 置村 健二郎, 小林 雄太, 中村 俊宏, Sakisaka Toshiaki
    BMB2010, Dec. 2010, Japanese, 日本分子生物学会・日本生化学会, 神戸, Domestic conference
    Oral presentation

  • Extensive search for crystallization condition of afadin PDZ domain
    藤原 芳江, 合田(天野, 名都子, 里村 香織, Sakisaka Toshiaki, 鈴木 守, 廣明 秀一
    グローバルCOE「統合的膜生物学の国際研究教育拠点」第4回ワークショップ, Jul. 2010, Japanese, 神戸大学, 淡路島, Domestic conference
    Poster presentation

  • Involvement of RA-RhoGAP in dendritic spine formation
    黒岡 貴生, Yamamoto Yasunori, Sakisaka Toshiaki
    第32回日本分子生物学会, Dec. 2009, Japanese, 日本分子生物学会, 横浜, Domestic conference
    Poster presentation

  • Reciprocal intramolecular interactions of tomosyn regulate neurotransmitter release
    Yamamoto Yasunori, 持田 澄子, 黒岡 貴生, Sakisaka Toshiaki
    第82回日本生化学会, Oct. 2009, Japanese, 日本生化学会, 神戸, Domestic conference
    Poster presentation

  • A novel inhibitory role of tomosyn against SNARE complex: implications for neurotransmitter release
    Sakisaka Toshiaki
    第61回日本細胞生物学会, Jun. 2009, English, 日本細胞生物学会, 名古屋, Domestic conference
    [Invited]
    Invited oral presentation

  • Involvement of afadin in the synaptogenesis of mouse hippocampal neurons
    出来祐子, Togashi Hideru, Sakisaka Toshiaki, Takai Yoshimi
    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, 日本分子生物学会日本生化学会, 神戸, Domestic conference
    Poster presentation

  • Vesicle transport-dependent Rap1 activation and its implication in neurite outgrowth
    Sakisaka Toshiaki, Takai Yoshimi
    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, English, 日本分子生物学会 日本生化学会, 神戸, Domestic conference
    Oral presentation

  • Vesicle transport-dependent Rap1 activation and its implication in neurite outgrowth
    Sakisaka Toshiaki, Takai Yoshimi
    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, English, 日本分子生物学会日本生化学会, 神戸, Domestic conference
    Oral presentation

  • Roles and modes of action of nectins and afadin in synaptogenesis
    Takai Yoshimi, Sakisaka Toshiaki, Togashi Hideru
    FENS 2008 Satellite Symposium, Jul. 2008, English, EPFL School of Life Sciences, Villars-sur-Ollon, スイス, International conference
    [Invited]
    Invited oral presentation

  • 小胞輸送によるRap1の活性化機構と軸索形成への関与
    Sakisaka Toshiaki, Takai Yoshimi
    第40回日本発生生物学会・第59回日本細胞生物学会合同大会, May 2007, Japanese, 日本発生生物学会、日本細胞生物学会, 福岡, Domestic conference
    [Invited]
    Invited oral presentation

■ Research Themes
  • Study on molecular mechanisms of fluidity of the endoplasmic reticulum
    匂坂 敏朗
    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Kobe University, 01 Apr. 2021 - 31 Mar. 2024
    小胞体は、細胞内に網目状に張り巡らせたチューブ構造と核膜周辺にあるシート構造からなる。この二つの構造は静的なものではなく、流動的であり、チューブ構造からシート構造、その逆のシート構造からチューブ構造に速やかに変化することが知られている。その異常が神経変性疾患の発症に関わるとされているが、その因果関係は十分明らかになっていない。したがって、小胞体流動の解明は生命現象の根幹に迫るきわめて重要な課題である。本研究では、小胞体流動の分子実態は、チューブ構造、シート構造、それぞれに関わるタンパク質の小胞体膜への挿入と解離による小胞体の構造制御タンパク質のホメオスタシスと捉え、それぞれの膜挿入装置と膜解離因子の単離、同定を行う。同定したタンパク質と人工膜を用いた試験管内再構成系を用いて小胞体流動を再現すると共に、その異常である神経変性疾患の発症との機能関係を明らかにし、小胞体流動の革新的な概念を提示する。 Lunaparkは小胞体のthree-way junctionに局在する膜タンパク質であり、私どもはlunaparkのユビキチンリガーゼ活性が小胞体の形態形成に必須の役割をしていることを明らかにしている。したがってlunaparkによるユビキチン化反応が膜解離の開始因子となり、小胞体流動を調節している可能性が考えられる。そこで本年度はlunaparkがユビキチン化する小胞体膜タンパク質の探索を行い、以下の結果を得た。 1)Lunaparkが小胞体膜タンパク質p63を選択的にユビキチン化することを見出した。 2)Lunaparkをノックダウンした培養細胞では、p63のプロテアソームによる分解が減少した。 p63は小胞体の選択的オートファジーであるERファジーを制御することが知られている。このことから、小胞体流動における膜解離因子がERファジーの調節因子と連携していると考えられた。

  • 匂坂 敏朗
    学術研究助成基金助成金/挑戦的萌芽研究, Apr. 2016 - Mar. 2019, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費一部基金/基盤研究(B), Apr. 2013 - Mar. 2018, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/新学術領域研究, Apr. 2014 - Mar. 2016, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    学術研究助成基金助成金/挑戦的萌芽研究, Apr. 2013 - Mar. 2016, Principal investigator
    Competitive research funding

  • 細胞接着装置構成タンパク質の構造生物学的研究
    匂坂 敏朗
    ターゲットタンパク研究プログラム, 2011, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/基盤研究(C), 2010, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/特定領域研究, 2008, Principal investigator
    Competitive research funding

  • 高井 義美
    科学研究費補助金/特定領域研究, 2008
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/基盤研究(C), 2007, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/特定領域研究, 2007, Principal investigator
    Competitive research funding

  • 匂坂 敏朗
    科学研究費補助金/特定領域研究, 2007, Principal investigator
    Competitive research funding

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