Search for novel membrane trafficking pathway involved in autophagy

2012 Fiscal Year Final Research Report

• Project/Area Number: 23770216
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: ITOH Takashi 東北大学, 大学院・生命科学研究科, 助教 (50373270)
• Project Period (FY): 2011 – 2012
• Keywords: タンパク質分解 / 膜輸送

Research Abstract

Macroautpohagy (referred to as autophagy hereafter) accompanies dynamic membrane remodeling such as autophagosome formation and fusion between autophagosome and lysosome. However, the regulation of such membrane remodeling is largely unknown. Since I had identified three Rab-GAPs, inactivators of Rab-type small GTPases, as autophagosome resident proteins, here I addressed the function of these Rab-GAPs (OATL1/TBC1D25, TBC1D2B, TBC1D11) in autophagy. They were localized at autophagosomes and bound with LC3, an autophagosome resident protein used as a marker of autophagosome. TBC1D2B and TBC1D25 required the interaction with LC3 for their localization at autophagosomes, since a point mutation that abolished the interaction impaired their localization. Although I previously revealed that overexpression of TBC1D25 inhibits fusion between autophagosomes and lysosomes, overexpression of TBC1D2B nor TBC1D11 did not inhibit any process of autophagy.
These results so far did not clarify relationship between these Rab-GAPs and autophagy. However, I suppose that it is possible that LC3 acts as a scaffold for Rab-GAPs and has a role in membrane trafficking in addition to in autophagy.

Research Products

• [Journal Article] Fis1 acts as mitochondrial recruitment factor for TBC1D15 that involved in regulation of mitochondrial morphology (2012)
  • Author(s): Onoue, K., Jofuku, A., Ban-Ishihara, R., Ishihara, T., Maeda, M., Koshiba, T., Itoh, T., Fukuda, M., Otera, H., Oka, T., Takano, H., Mizushima, N., Mihara, K., and Ishihara, N.
  • Journal Title: J. Cell Sci Volume: 126 Pages: 176-185
  • DOI: doi:10.1242/jcs.111211
  • Peer Reviewed
• [Journal Article] Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an Atg12-5-16L2complex (2011)
  • Author(s): Ishibashi, K., Fujita, N., Kanno, E., Omori, H., Yoshimori, T., Itoh, T. and Fukuda, M
  • Journal Title: Autophagy Volume: 7 Pages: 1500-1513
  • DOI: doi:10.4161/auto.7.12.18025
  • Peer Reviewed
• [Journal Article] Small GTPase Rab12 regulates constitutive degradation of transferrin receptor (2011)
  • Author(s): Matsui, T., Itoh, T., and Fukuda, M.
  • Journal Title: Traffic Volume: 12 Pages: 1432-1443
  • DOI: doi:10.1111/j.1600-0854.2011.01240.x
  • Peer Reviewed
• [Journal Article] A possible role of Atg8 homologs as a scaffold for signal transduction (2011)
  • Author(s): Itoh, T. and Fukuda, M
  • Journal Title: Autophagy Volume: 7 Pages: 1080-1081
  • DOI: doi:10.1126/science.1214081
  • Peer Reviewed
• [Presentation] A possible regulation of Rab33B-dependent membrane trafficking by the Atg12-5/16L1 complex (2012)
  • Author(s): Itoh, T., Fujita, N., Saitoh, T., Komatsu, M, Akira, S., Yoshimori, T., and Fukuda, M.
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] オートファジーに関わるRab不活性化因子の探索 (2011)
  • Author(s): 伊藤敬
  • Organizer: メンブレントラフィックのささやかな集い
  • Place of Presentation: 東北大加齢研
  • Year and Date: 2011-11-18
• [Presentation] Functional Analysis of Rab33B in Autophagy (2011)
  • Author(s): Itoh, T.
  • Organizer: 3rd UCL-Tohoku Univ. Symposium
  • Place of Presentation: London, UK
  • Year and Date: 2011-10-19