Functional analysis of the WD repeats domain in Atg16L which associates with Crohn disease

• Project/Area Number: 20870027
• Research Category: Grant-in-Aid for Young Scientists (Start-up)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Osaka University
• Principal Investigator: FUJITA Naonobu Osaka University, 微生物病研究所, 特任研究員 (00506496)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
• Keywords: オートファジー / Atg16L / WDリピートドメイン / クローン病

Research Abstract

Recent genome-wide association studies have linked autophagy, an intracellular bulk degradation system essential for diverse physiological process, with Crohn's disease, a major form of chronic inflammatory bowel disease. Single nucleotide polymorphisms in Atg16L (T300A) is a risk factor for Crohn's disease. However, it has been ill defined how the Atg16L variant confers the development of the disease. We demonstrate that Atg16L is a critical regulator of autophagy responsible for the control of the endotoxin-mediated immune response ; its dysfunction may be associated with inflammatory diseases such as colitis. Furthermore, we provide the first evidence that deletion of WD repeat domain and T300A mutation in Atg16L1 have little impact on canonical autophagy and autophagy against bacteria, Salmonella typhimurium. We therefore propose that Atg16L1 T300A is differentially involved in Crohn's disease and canonical autophagy.

Research Products

• [Journal Article] Combinational SNARE 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 (In press)
  • 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. (In press)
  • Peer Reviewed
• [Journal Article] Differencial involvement of ATG16L1 in Crohn's disease and canonical autophagy: analysis of the organization of the ATG16L1 complex in fibroblasts. (2009)
  • Author(s): Fujita, N., Saitoh, T., Kageyama, S., Akira, S., Noda, T., Yoshimori, T.
  • Journal Title: J Biol Chem. 284 Pages: 32602-32609
  • Peer Reviewed
• [Journal Article] Atg9a controls dsDNA-driven dynamic translocation of STING and the innate 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.
  • Journal Title: Proc Natl Acad Sci U S A 106 Pages: 20842-20846
  • 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., Yoshimori, T., Yamamoto, A.
  • Journal Title: Nature Cell Biology. 11 Pages: 1433-1437
  • Peer Reviewed
• [Journal Article] Differencial involvement of ATG16L1 in Crohn's disease and canonical autophagy : analysis of the organization of the ATG16L1 complex in fibroblasts. (2009)
  • Author(s): Fujita, N., Saitoh, T., Kageyama, S., Akira, S., Noda, T., Yoshimori, T.
  • Journal Title: J Biol Chem 284 Pages: 32602-32609
  • 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., Yoshimori, T., Yamamoto, A.
  • Journal Title: Nature Cell Biology 11 Pages: 1433-1437
  • Peer Reviewed
• [Journal Article] Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immuneresponse. (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.(*contributed equally)
  • Journal Title: Proc Natl Acad Sci USA (In press)
  • Peer Reviewed
• [Journal Article] Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1b production. (2008)
  • Author(s): Saitoh, T. *, Fujita, N. *, Jang, M., Uematsu, S., Yang, B., Satoh, T., Omori, H., Noda, T., Yamamoto, N., Komatsu, M., Tanaka, K., Kawai, T., Tsujimura, T., Takeuchi, O., Yoshimori, T., Akira, S.
  • Journal Title: Nature. 456 Pages: 264-268
  • Peer Reviewed
• [Journal Article] The Atgl6L Complex Specifies the Site of LC3 Lipidation forMembrane Biogenesis in Autophagy・ (2008)
  • Author(s): Fujita N, It oh T, Fukuda M, Noda T, Yoshimori T.
  • Journal Title: Mol Biol Cell. 19 Pages: 2092-2100
  • Peer Reviewed
• [Journal Article] Golgi-resident small GTPase Rab33B interacts with Atgl6L andmodulates autophagosome formation. (2008)
  • Author(s): Itoh T, Fujita N, Kanno E, Yamamoto A, Yoshimori T, Fukuda M.
  • Journal Title: Mol Biol Cell. 19 Pages: 2916-2925
  • Peer Reviewed
• [Journal Article] An Atg4B Mutant Hampers the Lipidation of LC3 Paralogues and Causes Defects in Autophagosome Closure. (2008)
  • Author(s): Fuiita N, Hayashi M, Fukumoto H, Omori H, YamamotoA, Noda T, Yoshimori T.
  • Journal Title: Mol Biol Cell. 19 Pages: 4651-4659
  • Peer Reviewed
• [Journal Article] Loss of the autophagy protein Atgl6Ll enhances endotoxin-induced IL-lbeta production. (2008)
  • Author(s): Saitoh T*, Fujita N*, JangMH, Uematsu s, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, Tanaka K, Kawai T, TsujimuraT, Takeuchi o, YoshimoriT, Akira S. (*These authorscontributed equally to this work. )
  • Journal Title: Nature. 456 Pages: 264-268
  • Peer Reviewed
• [Presentation] DIFFERENTIAL INVOLVEMENT OF Atg16L1 IN CROHN'S DISEASE AND CANONICAL AUTOPHAGY : ANALYSIS OF ORGANIZATION OF THE Atg16L1 COMPLEX (2009)
  • Author(s): 藤田尚信
  • Organizer: 5th International Symposium on Autophagy
  • Place of Presentation: 大津プリンスホテル
  • Year and Date: 2009-09-25
• [Presentation] Functional analysis of the Atg16L complex essential for mammalian autophagy (2009)
  • Author(s): 藤田尚信
  • 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: 2009-06-03
• [Book] メンブレントラフィックの奔流 (2008)
  • Author(s): 藤田尚信, 他
  • Publisher: 共立出版
• [Book] メンブレントラフィックの奔流 (2008)
  • Author(s): 藤田尚信
  • Publisher: 共立出版
• [Remarks] ホームページ等
  • URL: http://www.saibouseigyo.com/jp/
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/act/act_yoshimori.php
• [Remarks]
  • URL: http://www.biken.osaka-u.ac.jp/act/act_yoshimori.php