オートファジーによる生存戦略の分子基盤

2009 Fiscal Year Annual Research Report

• Project/Area Number: 19207015
• Research Institution: Osaka University
• Principal Investigator: 吉森 保 Osaka University, 微生物病研究所, 教授 (60191649)
• Keywords: オートファジー / 生存戦略 / 小胞体 / 電子線トモグラフィー / Atgタンパク質 / インタラクトーム / エンドソーム・リソソーム / 膜の損傷

Research Abstract

オートファジーは、真核生物に普遍的な細胞内大規模分解システムとして、飢餓時の栄養源確保から病原体排除まで多彩な機能を持つ。これらの機能の多くは生命維持に関わっており、オートファジーの多面的活川による生存戦略が存在するといえよう。オートファジーの役割の解明が進む一方で、その分子機構はいまだ謎が多い。本研究課題では、生存戦略としてのオートファジーという観点からその分子解剖を行う。本年度は以下の成果を得た。
1. 長浜バイオ大・山本章嗣教授らとの共同研究により、オートファゴソームが小胞体の局所に形成される特殊な「ゆりかご」状構造で形成きれ、そこでは小胞体膜と形成途上のオートファゴソーム膜が連続していることを電子線トモグラフィーで明らかにした。長年の論争の的であるオートファゴソームの起源を知る大きな手がかりとなるものである。
2. 既知の全てのオートファジー関連タンパク質Atgについて、インタラクトーム解析及び結合タンパク質解析を行い、新規の相互結合関係と新規結合タンパク質を複数発見した。
3. ある種のウイルスが宿主細胞からの放出時にオートファジーを利用している可能性を示唆する予備データを得た。
4. 薬剤などでエンドソーム・リソソームの膜を損傷すると、そこにオートファゴソームマーカーのLC3が集積することを見出した。損傷オルガネラの修復あるいは除去にオートファジーが働いている可能性がある。

Research Products

• [Journal Article] Artificial induction of autophagy around polystyrene beads in nonphagocytic cells. (2010)
  • Author(s): Kobayashi S, Kojidani T, Osakada H, Yamamoto A, Yoshimori T, Hiraoka Y, Haraguchi T*.
  • Journal Title: Autophagy. 6 Pages: 36-45
  • Peer Reviewed
• [Journal Article] Modulation of local PtdIns3P levels by the Pl phosphatase MTMR3 regulates constitutive autophagy. (2010)
  • Author(s): Taguchi-Atarashi N, Hamasaki M, Matsunaga K, Omori H, Ktistakis NT, Yoshimori T, Noda T*.
  • Journal Title: Traffic. 11(4) Pages: 468-478
  • Peer Reviewed
• [Journal Article] Combinational Soluble N-Ethylmaleimide-sensitive Factor Attachment Protein Receptor Proteins VAMP8 and Vtilb Mediate Fusion of Antimicrobial and Canonical Autophagosomes with Lysosomes. (2010)
  • Author(s): Furuta N, Fujita N, Noda T, Yoshimori T, Amano A*.
  • Journal Title: Mol Biol Cell. 21 Pages: 1001-1010
  • Peer Reviewed
• [Journal Article] Autophagosome can support Yersinia pseudotuberculosis replication in macrophages. (2010)
  • Author(s): Moreau K, Lacas-Gervais S, Fujita N, Sebbane F, Yoshimori T, Simonet M, Lafont F*.
  • Journal Title: Cell Microbiol. (Feb 23. [Epub ahead of print])
  • Peer Reviewed
• [Journal Article] Two Beclin-1 binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. (2009)
  • Author(s): Matsunaga K, Saitoh T, Tahata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura I, Isobe T, Akira S, Noda T, Yoshimori T*.
  • Journal Title: Nature Cell Biol 11 Pages: 385-396
  • Peer Reviewed
• [Journal Article] Autophagic Elimination of Misfolded Procollagen Aggregates in the Endoplasmic Reticulum as a Means of Cell Protection. (2009)
  • Author(s): Ishida Y, Yamamoto A, Kitamura A, Lamande S, Yoshimori T, Bateman J, Kubota H, Nagata K*.
  • Journal Title: Mol Biol Cell. 20 Pages: 2744-2754
  • Peer Reviewed
• [Journal Article] Differencial involvement of ATG 16Ll in Crohn's disease and canonical autophagy : analysis of the organization of the ATG 16Ll complex in fibroblasts. (2009)
  • Author(s): Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, Yoshimori T*.
  • Journal Title: J Brol Chem. 284 Pages: 32602-21609
  • Peer Reviewed
• [Journal Article] Cochaperone activity of human butyrate-induced transcript 1 facilitates hepatitis C virus replication through an Hsp90-dependent pathway. (2009)
  • Author(s): Taguwa S, Kambara H, Omori H, Tani H, Abe T, Mori Y, Suzuki T, Yoshimori T, Moriishi K, Matsuura Y*.
  • Journal Title: J Virol. 83 Pages: 10427-10436
  • Peer Reviewed
• [Journal Article] Porphyromonas gingivalis outer membrane vesicles enter human epithelial cells via an endocytic pathway and are sorted to lysosomal compartments. (2009)
  • Author(s): Furuta N, Tsuda K, Omori H, Yoshimori T, Yoshimura F, Amano A*.
  • Journal Title: Infect Immun. 77 Pages: 4187-4196
  • Peer Reviewed
• [Journal Article] The Stent-Eluting Drugs Sirolimus and Paclitaxel Suppress Healing of the Endothelium by Induction of Autophagy. (2009)
  • Author(s): Hayashi SI, Yamamoto A, You F, Yamashita K, Ikegame Y, Tawada M, Yoshimori T, Shimizu S, Nakashima S*.
  • Journal Title: Am J Pathol. 175 Pages: 2226-2234
  • Peer Reviewed
• [Journal Article] A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. (2009)
  • Author(s): Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimon T*, Yamamoto A*.
  • Journal Title: Nat Cell Biol. 11 Pages: 1433-1437
  • Peer Reviewed
• [Journal Article] Atg9a controls dsDNA-driven dynamic translocation of STING and the ornate immune response. (2009)
  • Author(s): Saitoh T§, Fujita N§, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T, Yamamoto N, Kawai T, Ishii K, Takeuchi O, Yoshimori T, Akira S*. (§These authors contributed equ|ally to this work. )
  • Journal Title: Proc Natl Acad Sci USA. 106(49) Pages: 20842-20846
  • Peer Reviewed
• [Journal Article] An initial step of GAS-containing autophagosome-like vacuoles formation requires Rab7. (2009)
  • Author(s): Yamaguchi H, Nakagawa I, Yamamoto A, Amano A, Noda T, Yoshimori T*.
  • Journal Title: PLoS Puthog. 5 Pages: e1000670. doi : 10.1371/journal.ppat.1000670
  • Peer Reviewed
• [Journal Article] (2009)
  • Author(s): Yoshimori T, Amano A.
  • Journal Title: Curr Top Microbiol Imnunol. 335(Springer) Pages: 217-226
• [Presentation] Membrane Biogenesis and Regulatory Mechanisms in Autophagy (2009)
  • Author(s): 吉森保
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 20091209-20091212
• [Presentation] Binding Rubicon to Cross the Rubicon (2009)
  • Author(s): Tamotsu Yoshimori
  • Organizer: EMBO Conference on : Autophagy, Cell Biology, Physiology and Pathology
  • Place of Presentation: Monte Verity, Ascona, Switzerland
  • Year and Date: 20091018-20091021
• [Presentation] Beclinl Complexes, Salmonella, and Atg16L (2009)
  • Author(s): 吉森保
  • Organizer: 5th International Symposium on Autophagy
  • Place of Presentation: 大津プリンスホテル
  • Year and Date: 20090924-20090928
• [Presentation] Autophagy : Molecular Machinery and Roles in Diseases (2009)
  • Author(s): Tamotsu Yoshimori
  • Organizer: The 7th CBD (ARC Centre of Excellence in Biotechnology & Development) Scientific Meeting
  • Place of Presentation: The Country Place Retreat, Kalorama, Victoria, Australia
  • Year and Date: 20090906-20090909
• [Presentation] Mechanistic Insight into Membrane Dynamics in Mammalian Autophagy (2009)
  • Author(s): Tamotsu Yoshimori
  • Organizer: Gordon Research Conference Molecular Membrane Biology
  • Place of Presentation: Proctor Academy, Andaver, NH, USA
  • Year and Date: 20090705-20090710
• [Presentation] Tuning Autophagy and Heterophagy (2009)
  • Author(s): 吉森保
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 20090602-20090604
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/act/act_yoshimori.php