Analysis of intracellular pathogenic pathway of Legionella pneumophila

• Project/Area Number: 26713016
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Bacteriology (including mycology)
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Arasaki Kohei 東京薬科大学, 生命科学部, 講師 (70609990)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: レジオネラ / レジオネラエフェクター / Rabタンパク質 / 小胞輸送 / 小胞体 / 膜輸送 / ユビキチン / 小胞体サブドメイン / Bap31 / リソソーム / エフェクター / 細胞内小胞輸送 / プロテアソーム

Outline of Final Research Achievements

In this research, we demonstrated following three things. 1: Legionella manipulates Rab33b-Rab6 cascade to escort LCV to the host ER and we identified the candidate effectors that recruits Rab33b to the Legionella containing vacuole (LCV). 2: After internalization into host cells, Legionella blocks delivery of LCV to the lysosomal compartment. In this process, Legionella degrades Rab5 by ubiquitin dependent manner and we identified E3 ligase like effector against Rab5. 3: It is known that Legionella replicates inside host ER. In this process, we demonstrated that Legionella first associates and fuses with smooth ER to evade host ER. Subsequently, Legionella moves to rough ER and starts to replicates. In this traffic, we identified the host protein that requires traffic of Legionella from the smooth to the rough ER. Furthermore, we also identified the candidate effector that subverts this host factor.

Research Products

• [Journal Article] Syntaxin 17 promotes lipid droplet formation by regulating the distribution of acyl-CoA synthetase 3. (2018)
  • Author(s): Kimura H, Arasaki K, Ohsaki Y, Fujimoto T, Ohtomo T, Yamada J, Tagaya M.
  • Journal Title: J Lipid Res. Volume: in press Issue: 5 Pages: 805-819
  • DOI: 10.1194/jlr.m081679
  • Peer Reviewed
• [Journal Article] Legionella blocks autophagy by cleaving STX17 (syntaxin 17). (2017)
  • Author(s): Arasaki K, Tagaya M.
  • Journal Title: Autophagy. Volume: 13 Issue: 11 Pages: 2008-2009
  • DOI: 10.1080/15548627.2017.1371395
  • Peer Reviewed / Open Access
• [Journal Article] Legionella effector Lpg1137 shuts down ER-mitochondria communication through cleavage of syntaxin 17. (2017)
  • Author(s): Arasaki K, Mikami Y, Shames SR, Inoue H, Wakana Y, Tagaya M.
  • Journal Title: Nat Commun. Volume: 15406 Issue: 1 Pages: 1-12
  • DOI: 10.1038/ncomms15406
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Regulation of Mitochondrial Dynamics and Autophagy by the Mitochondria-Associated Membrane. (2017)
  • Author(s): Tagaya M, Arasaki K.
  • Journal Title: Adv Exp Med Biol. Volume: 997 Pages: 33-47
  • DOI: 10.1007/978-981-10-4567-7_3
  • ISBN: 9789811045660, 9789811045677
• [Journal Article] Legionella Effector Lpg1137 Shuts down ER-mitochondria Communication through Cleavage of Syntaxin 17 (2017)
  • Author(s): Arasaki K., Mikami Y., Shames SR., Inoue H., Wakana Y., Tagaya M.
  • Journal Title: Nature Communications Volume: in press
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [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] CARTS biogenesis requires VAP-lipid transfer protein complexes functioning at the endoplasmic reticulum-Golgi interface. (2015)
  • Author(s): Wakana Y., Kotake R., Oyama N., Murate M., Kobayashi T., Arasaki K., Inoue H., Tagaya M.
  • Journal Title: Mol. Biol Cell Volume: 26 Issue: 25 Pages: 4686-4699
  • DOI: 10.1091/mbc.e15-08-0599
  • Peer Reviewed / Open Access
• [Journal Article] Role for the ancient SNARE syntaxin 17 in regulating mitochondrial division. (2015)
  • Author(s): Arasaki, K., Shimizu, H., Mogari, H., Nishida, N., Hirota, N., Furuno, A., Kudo, Y., Baba, M., Baba, N., Cheng, J., Fujimoto, T., Ishihara, N., Ortiz-Sandoval, C., Barlow, L. D., Raturi, A., Dohmae, N., Wakana, Y., Inoue, H., Tani, K., Dacks, J. B., Simmen, T., and Tagaya, M.
  • Journal Title: Developmental Cell Volume: 32 Pages: 304-317
  • Peer Reviewed
• [Journal Article] The machinery at endoplasmic reticulum-plasma membrane contact sites contributes to spatial regulation of multiple Legionella effector proteins. (2014)
  • Author(s): Hubber, A., Arasaki, K., Nakatsu, F., Hardiman, C.,Lambright, D., De Camilli, P., Nagai, H., and Roy, C. R.
  • Journal Title: PLoS Pathogens Volume: 10
  • 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: Journal of Biologicalchemistery Volume: 289 Pages: 24304-24313
  • Peer Reviewed
• [Presentation] Syntaxin 17はACSL3の局在と機能を制御することで脂肪滴形成を促進する (2018)
  • Author(s): 新崎恒平・木村葉那・大崎雄樹・多賀谷光男
  • Organizer: 第１２３回 日本解剖学会総会 シンポジウム
• [Presentation] Legionella Effector Lpg1137 Shuts down ER-mitochondria Communication through Cleavage of Syntaxin 17 (2017)
  • Author(s): 新崎恒平、三上優美、James Havey、Stephanie Shames、Craig Roy、多賀谷光男
  • Organizer: 第９０回 日本細菌学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-19
• [Presentation] レジオネラはsyntaxin 17の分解を介して宿主防御機構を回避する (2017)
  • Author(s): 新崎恒平
  • Organizer: 第１００回 日本細菌学会関東支部総会 シンポジウム
  • Invited
• [Presentation] 小胞体－ミトコンドリア接触部位におけるsyntaxin 17の多彩な生理機能 (2017)
  • Author(s): 新崎恒平、多賀谷光男
  • Organizer: 第９０回 日本生化学会大会 ワークショップ
  • Invited
• [Presentation] 小胞体SNAREタンパク質の多様な機能 (2017)
  • Author(s): 新崎恒平
  • Organizer: 第９０回 日本生化学会大会 受賞記念講演
  • Invited
• [Presentation] MAP1B-LC1による脂肪滴形成の制御 (2017)
  • Author(s): 木村葉那、新崎恒平、大崎雄樹、多賀谷光男
  • Organizer: 第９０回 日本生化学会大会 ポスター発表
• [Presentation] Syntaxin 17 promotes lipiddroplet formation by regulating the distribution of ACSL3, a key enzyme for lipid droplet biogenesis. (2016)
  • Author(s): Hana Kimura, Kohei Arasaki, Mitsuo Tagaya
  • Organizer: 2016 American Society of Cell Biology
  • Place of Presentation: San francisco
  • Year and Date: 2016-12-03
• [Presentation] MAP1B-LC1 regulates autophagosome formation by interacting with the autophagy-related SNARE syntaxin 17 (2016)
  • Author(s): Kohei Arasaki, Mitsuo Tagaya, Naoshi Dohmae, Yuri Kurosawa, Haruki Nagashima
  • Organizer: 2016 American Society of Cell Biology
  • Place of Presentation: San francisco
  • Year and Date: 2016-12-03
• [Presentation] The autophagic function of syntaxin 17 is suppressed by MAP1B-LC1 (2016)
  • Author(s): 新崎恒平、 長島晴輝、 黒澤優里、 堂前直、多賀谷光男
  • Organizer: 第８９回 日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
  • Invited
• [Presentation] Syntaxin 17 regulates the lipid droplets localization of ACSL3 through interaction with SNAP-23 (2016)
  • Author(s): 木村葉那、 新崎恒平、 多賀谷光男
  • Organizer: 第８９回 日本生化学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2016-09-25
• [Presentation] 脂肪滴形成におけるMAMの役割～Stx17の機能を中心として～ (2016)
  • Author(s): 新崎 恒平、木村 葉那、大崎 雄樹、多賀谷 光男
  • Organizer: 第１２１回 日本解剖学会総会
  • Place of Presentation: ビックパレットふくしま
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Stx17はACSL3を制御することで脂肪滴形成に関与する (2016)
  • Author(s): 木村 葉那、新崎 恒平、大崎 雄樹、多賀谷 光男
  • Organizer: 第１２１回 日本解剖学会総会
  • Place of Presentation: ビックパレットふくしま
  • Year and Date: 2016-03-28
• [Presentation] Rab6A and Rab33B function in Legionella infection (2016)
  • Author(s): 川端 美緒、多賀谷 光男、新崎 恒平
  • Organizer: 第８９回 日本細菌学会総会
  • Place of Presentation: 大阪国際交流センター
  • Year and Date: 2016-03-23
• [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８８回 日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • 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８８回 日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] レジオネラ菌感染に関わる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] 脂肪滴形成および3T3-L1の脂肪細胞への分化におけるsyntaxin 17の関与 (2014)
  • Author(s): 木村葉那、新崎恒平、茂刈寛史、谷佳津子、多賀谷光男
  • Organizer: 第66回日本細胞生物学会大会
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-11 – 2014-06-13