Roles of syntaxin 17 in the formation and function of the mitochondria-associated ER membrane

• Project/Area Number: 25291029
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TAGAYA MITSUO 東京薬科大学, 生命科学部, 教授 (30179569)
• Co-Investigator(Kenkyū-buntansha): INOUE Hiroki 東京薬科大学, 生命科学部, 講師 (10294448) ; HASHIMOTO Yoshitami 東京薬科大学, 生命科学部, 助教 (50616761) ; ARASAKI Kohei 東京薬科大学, 生命科学部, 講師 (70609990)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 小胞体 / ミトコンドリア / syntaxin17 / レジオネラ / 神経変性疾患

Outline of Final Research Achievements

The MAM（mitochondria-associated membrane）is one of the subdomains of the ER and participates in various cellular phenomena. We found that syntaxin 17 (Syn17) is localized in the MAM and plays the following functions: (1) Syn17 promotes mitochondrial fission by defining the localization and activity of the mitochondrial fission factor Drp1. (2) Syn17 regulates Ca2+ homeostasis of the ER. (3) Syn17 regulates the localization of PGAM5, a protein phosphatase for Drp1. (4) MAP1B-LC1 mediates the link of Syn17 with microtubules and Drp1. (5) Upon infection, Legionella degrades Syn17, and one of its effectors is responsible for this degradation.

Research Products

• [Journal Article] γ-SNAP stimulates disassembly of endosomal SNARE complexes and regulates endocytic trafficking pathways. (2015)
  • Author(s): Inoue, H., Matsuzaki, Y., Tanaka, A., Hosoi, K., Ichimura, K., Arasaki, K., Wakana, Y., Asano, K., Tanaka, M., Okuzaki, D., Yamamoto, A., Tani, K. and Tagaya, M.
  • Journal Title: J. Cell Sci. Volume: 128 Pages: 2781-2794
  • DOI: 10.1242/jcs.158634
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 変わりゆくオルガネラ間コミュニケーションの概念 (2015)
  • Author(s): 多賀谷光男
  • Journal Title: 実験医学 Volume: 33 Pages: 2546-2552
• [Journal Article] MAM-ミトコンドリア機能を制御する小胞体サブドメイン (2015)
  • Author(s): 多賀谷光男、新崎恒平、谷佳津子
  • Journal Title: 実験医学 Volume: 33 Pages: 2553-2559
• [Journal Article] A Role for the Ancient SNARE Syntaxin 17 in Regulating Mitochondrial Division (2015)
  • Author(s): K. Arasaki, H. Shimizu, H. Mogari, N. Nishida, N. Hirota, A. Furuno, Y. Kudo, M. Baba, N. Baba, J. Cheng, T. Fujimoto, N.Ishihara, C. Ortiz-Sandoval, L. Barlow, A Raturi, N. Dohmae, Y. Wakana, H. Inoue, K.Tani, J. Dacks, T.Simmen, M. Tagaya
  • Journal Title: Developmental Cell Volume: 32(9) Issue: 3 Pages: 304-317
  • DOI: 10.1016/j.devcel.2014.12.011
  • Peer Reviewed
• [Journal Article] Valosin-containing protein-interacting membrane protein (VIMP) links the endoplasmic reticulum with microtubules in concert with cytoskeleton-linking membrane protein (CLIMP)-63 (2014)
  • Author(s): Noda, C., Kimura, H., Arasaki, K., Matsushita, M., Yamamoto, A., Wakana, Y., Inoue, H., and Tagaya, M.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 35 Pages: 24304-24313
  • DOI: 10.1074/jbc.m114.571372
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Moonlighting functions of the NRZ (mammalian Dsl1) complex. Front (2014)
  • Author(s): Tagaya, M., Arasaki, K., Inoue, H., and Kimura, H.
  • Journal Title: Cell Develop. Biol Volume: (in press) Pages: 25-25
  • DOI: 10.3389/fcell.2014.00025
  • Peer Reviewed / Open Access
• [Journal Article] MAMの新たな機能と関連疾患 (2014)
  • Author(s): 2. 多賀谷光男、若菜裕一、川端美緒
  • Journal Title: 細胞工学 Volume: 33 Pages: 436-442
  • NAID: 40020031737
• [Journal Article] PtdIns(3)P-bound UVRAG coordinates Golgi-ER retrograde and Atg9 transport by differential interactions with the ER tether and the Beclin1 complex. (2013)
  • Author(s): He, S., Ni, D., Ma, B., Lee, J.-H., Zhang, T., Ghozalli, I., Pirooz, S. D., Zhao, Z., Bharatham, N., Li, B., Oh, S., Lee, W.-H., Takahashi, Y., Wang, H.-G., Minassian, A., Feng, P., Deretic, V., Pepperkok, R., Tagaya, M., Yoon, H. S., and Liang, C.
  • Journal Title: Nat. Cell Biol. Volume: 15 Issue: 10 Pages: 1206-1219
  • DOI: 10.1038/ncb2848
  • Peer Reviewed
• [Journal Article] A new role for RINT-1 in SNARE complex assembly at the trans-Golgi network in coordination with the COG complex. (2013)
  • Author(s): A new role for RINT-1 in SNARE complex assembly at the trans-Golgi network in coordination with the COG complex.
  • Journal Title: Mol Biol Cell Volume: 24 Issue: 18 Pages: 2907-2917
  • DOI: 10.1091/mbc.e13-01-0014
  • Peer Reviewed
• [Presentation] 脂肪滴の生合成形におけるsyntaxin 17の関与 (2015)
  • Author(s): 木村葉那、新崎恒平、多賀谷光男
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] MAP1B-LC1はsyntaxin17との相互作用を介してオートファジーを制御する (2015)
  • Author(s): 長島晴輝、新崎恒平、黒澤優里、堂前直、多賀谷光男
  • Organizer: 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
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] Regulation of mitochondrial division and mitophagy by syntaxin 17 (2015)
  • Author(s): Kohei Arasaki, Masashi Sugo, Naohiko Hirota, Naoshi Dohmae, Carolina Ortiz-Sandoval, Thomas Simmen, Yuzuru Imai, Nobutaka Hattori, and Mitsuo Tagaya
  • Organizer: Mutifaceted Mitochondria
  • Place of Presentation: Chicago
  • Year and Date: 2015-07-19
• [Presentation] Syntaxin17はDrp1の脱リン酸化酵素であるPGAM5の局在を調節する (2015)
  • Author(s): 須合真士、新崎恒平、堂前直、多賀谷光男
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] Syntaxin17の分解に関わるレジオネラエフェクターの探索 (2015)
  • Author(s): 三上優美、ハーベイ ジェームス、ロイ クレイグ、多賀谷光男、新崎恒平
  • Organizer: 第67回日本細胞生物学会大会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-30
• [Presentation] レジオネラ感染に関わるRabタンパク質の同定及びレジオネラ菌の小胞体定着化機構 (2015)
  • Author(s): 新崎恒平、川端美緒、加藤郁子、多賀谷光男
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-03-26 – 2015-03-28
  • Invited
• [Presentation] レジオネラ菌によるRab5ユビキチン化機構の解明 (2015)
  • Author(s): 川端美緒、加藤郁子、多賀谷光男、新崎恒平
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] レジオネラ菌は小胞体内での移行にRab4及びRab10を利用する (2015)
  • Author(s): 加藤郁子、川端美緒、新崎恒平、多賀谷光男
  • Organizer: 第88回日本細菌学会総会
  • Place of Presentation: 岐阜
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] レジオネラ菌の宿主小胞体への移行及び定着化の機構 (2014)
  • Author(s): 新崎恒平、川端美緒、野内優、多賀谷光男
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] PGAM5によるDrp1の脱リン酸化へのSyntaxin17の関与 (2014)
  • Author(s): 須合真士、新崎恒平、堂前直、多賀谷光男
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] レジオネラ菌の小胞体への侵入にはRab6が機能する (2014)
  • Author(s): 川端美緒、加藤郁子、新崎恒平
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] Rab4及びRab10のレジオネラ感染における機能解析 (2014)
  • Author(s): 加藤郁子、川端美緒、新崎恒平
  • Organizer: 第87回日本細菌学会総会
  • Place of Presentation: 東京
• [Presentation] RINT-1の新たな役割：COG複合体との協調によるTGN局在SNARE複合体の会合の調節 (2013)
  • Author(s): 新崎恒平、高木大地、古野暁子、相田美和、三角佳生、多賀谷光男
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
• [Presentation] 小胞体とミトコンドリアの接触部位におけるsyntaxin17の役割 (2013)
  • Author(s): 多賀谷光男、新崎恒平
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 浸潤突起形成に関わるSNAREタンパク質の探索 (2013)
  • Author(s): 青木瑶子、渡邉卓也、多賀谷光男、井上弘樹
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Remarks]
  • URL: http://pathos.ls.toyaku.ac.jp/?page_id=121
• [Remarks] 分子細胞生物学研究室のページ
  • URL: http://pathos.ls.toyaku.ac.jp/?page_id=121