Functional analysis of Rab GTPase-activating proteins that are recruited to autophagosomes

• Project/Area Number: 24370077
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: FUKUDA Mitsunori 東北大学, 生命科学研究科, 教授 (50311361)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: Rab / Rab不活性化因子 / 膜輸送 / Atg16L1 / オートファジー / 低分子量G蛋白質 / オルガネラ / 蛋白質分解

Outline of Final Research Achievements

It has recently been reported that several Rab GTPase-activating proteins (GAPs) localize autophagosomes, but their precise mechanisms of autophagosomal targeting and their functions in autophagy are poorly understood. In this study, we analyzed the LC3 recognition sequence of OATL1, a Rab33B-GAP, and its localization on autopagosomes. We found that OATL1 is specifically localized outside the autophagosomal membrane through interaction with LC3 and that such asymmetric localization enables OATL1 to regulate the autophagosomal maturation without OTAL1 being degraded by autophagy.

Research Products

• [Journal Article] Rab40C is a novel Varp-binding protein that promotes proteasomal degradation of Varp in melanocytes. (2015)
  • Author(s): Yatsu, A., Shimada, H., Ohbayashi, N. and Fukuda, M.
  • Journal Title: Biol. Open Volume: 4 Issue: 3 Pages: 267-275
  • DOI: 10.1242/bio.201411114
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP (2015)
  • Author(s): Ishida, M., Ohbayashi, N. and Fukuda, M
  • Journal Title: Sci. Rep. Volume: 5 Issue: 1 Pages: 8238-8238
  • DOI: 10.1038/srep08238
  • Peer Reviewed / Open Access
• [Journal Article] The GTPase-deficient Rab27A(Q78L) Mutant Inhibits Melanosome Transport in Melanocytes through Trapping of Slac2-a/melanophilin in their Cytosol: Development of a Novel Melanosome-targeting Tag (2014)
  • Author(s): Ishida, M., Arai, SP., Ohbayashi, N. and Fukuda, M
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 16 Pages: 11059-11067
  • DOI: 10.1074/jbc.m114.552281
  • Peer Reviewed
• [Journal Article] Rab35 is translocated from Arf6-positive perinuclear recycling endosomes to neurite tips during neurite outgrowth. (2014)
  • Author(s): Kobayashi H, Etoh K, Fukuda M
  • Journal Title: Small GTPases Volume: 5 Issue: 3 Pages: 1-4
  • DOI: 10.4161/sgtp.29290
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Small GTPase Rab17 regulates the surface expression of kainate receptors but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in hippocampal neurons via dendritic trafficking of Syntaxin-4 protein. (2014)
  • Author(s): Mori, Y., Fukuda, M. and Henley, J. M.
  • Journal Title: J. Biol. Chem. Volume: 289 Issue: 30 Pages: 20773-20787
  • DOI: 10.1074/jbc.m114.550632
  • Peer Reviewed
• [Journal Article] Rab35 promotes the recruitment of Rab8, Rab13, and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth. (2014)
  • Author(s): Kobayashi H, Etoh K, Ohbayashi N, Fukuda M
  • Journal Title: Biol Open Volume: 3 Issue: 9 Pages: 803-814
  • DOI: 10.1242/bio.20148771
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma membrane recycling. (2014)
  • Author(s): McGough, I. J., Steinberg, F., Gallon, M., Yatsu, A., Ohbayashi, N., Heesom, K., Fukuda, M. and Cullen, P. J.
  • Journal Title: J. Cell Sci. Volume: 127 Pages: 4940-4953
  • DOI: 10.1242/jcs.156299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] TBC1D9B functions as a GTPase-activating protein for Rab11a in polarized MDCK cells. (2014)
  • Author(s): Gallo, L. I., Liao, Y., Ruiz, W. G., Clayton, D. R., Li, M., Liu, Y.-J., Jiang, Y., Fukuda, M., Apodaca, G. and Yin, X.-M.
  • Journal Title: Mol. Biol. Cell Volume: 25 Issue: 23 Pages: 3779-3797
  • DOI: 10.1091/mbc.e13-10-0604
  • Peer Reviewed
• [Journal Article] メラノソームの微小管逆行輸送機構―白髪予防の新たな分子標的 (2014)
  • Author(s): 大林典彦、福田光則
  • Journal Title: フレグランスジャーナル (FRAGRANCE JOURNAL) Volume: 42 Pages: 30-35
• [Journal Article] Rab27 effectors, pleiotropic regulators in secretory pathways. (2013)
  • Author(s): Fukuda, M.
  • Journal Title: Traffic Volume: 14 Issue: 9 Pages: 949-963
  • DOI: 10.1111/tra.12083
  • Peer Reviewed
• [Journal Article] Rabex-5 determines the neurite localization of its downstream Rab proteins in hippocampal neurons. (2013)
  • Author(s): Mori, Y. and Fukuda, M.
  • Journal Title: Commun. Integr. Biol. Volume: 6 Issue: 5 Pages: e25433-e25433
  • DOI: 10.4161/cib.25433
  • Peer Reviewed
• [Journal Article] Syntaxin-3 is required for melanosomal localization of Tyrp1 in melanocytes (2013)
  • Author(s): Yatsu, A., Ohbayashi, N., Tamura, K.& Fukuda M
  • Journal Title: J. Invest. Dermatol Volume: (in press) Issue: 9 Pages: 2237-2246
  • DOI: 10.1038/jid.2013.156
  • Peer Reviewed
• [Journal Article] Rab35 establishes the EHD1-association site by coordinating two distinct effectors during neurite outgrowth. (2013)
  • Author(s): Kobayashi, H. and Fukuda, M.
  • Journal Title: J. Cell Sci. Volume: 126 Pages: 2424-2435
  • DOI: 10.1242/jcs.117846
  • Peer Reviewed
• [Journal Article] Small GTPase Rab39A interacts with UACA and regulates the retinoic acid-induced neurite morphology of Neuro2A cells (2013)
  • Author(s): Mori, Y., Matsui, T., Omote, D. and Fukuda, M.
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 435 Issue: 1 Pages: 113-119
  • DOI: 10.1016/j.bbrc.2013.04.051
  • Peer Reviewed
• [Journal Article] MADD/DENN/Rab3GEP functions as a guanine nucleotide exchange factor for Rab27 during granule exocytosis of rat parotid acinar cells. (2013)
  • Author(s): Imai A, Ishida M, Fukuda M, Nashida T, Shimomura H.
  • Journal Title: Arch Biochem Biophys Volume: 536 Issue: 1 Pages: 31-37
  • DOI: 10.1016/j.abb.2013.05.002
  • Peer Reviewed
• [Journal Article] Recruitment of the autophagic machinery to endosomes during infection is mediated by ubiquitin (2013)
  • Author(s): Naonobu Fujita et al.
  • Journal Title: J. Cell Biol. Volume: 203 Issue: 1 Pages: 115-128
  • DOI: 10.1083/jcb.201304188
  • Peer Reviewed / Open Access
• [Journal Article] Rab GTPases and their roles in membrane traffic. (2013)
  • Author(s): 大林典彦、福田光則
  • Journal Title: Leading Author's Volume: 2 Pages: e006
  • DOI: 10.7875/leading.author.2.e006
  • Peer Reviewed
• [Journal Article] Fis1 acts as mitochondrial recruitment of TBC1D15 that involved in regulation of mitochondrial morphology (2013)
  • Author(s): K. Onoue et al.
  • Journal Title: J. Cell Sci. Volume: 126 Issue: 1 Pages: 176-186
  • DOI: 10.1242/jcs.111211
  • Peer Reviewed
• [Journal Article] Atg16L1, an essential factor for canonical autophagy, participates in hormone secretion from PC12 cells independently of autophagic activity (2012)
  • Author(s): Ishibashi, K., Uemura, T., Waguri, S. & Fukuda, M
  • Journal Title: Mol. Biol. Cell Volume: 23 Issue: 16 Pages: 3193-3202
  • DOI: 10.1091/mbc.e12-01-0010
  • Peer Reviewed
• [Journal Article] Rab27 effector Slp2-a transports the apical signaling molecule podocalyxin to the apical surface of MDCK II cells and regulates claudin-2 expression. (2012)
  • Author(s): Yasuda T, et al.
  • Journal Title: Molecular Biology of the Cell Volume: 23 Issue: 16 Pages: 3229-3239
  • DOI: 10.1091/mbc.e12-02-0104
  • Peer Reviewed
• [Journal Article] Guideline for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ,et al
  • Journal Title: Autophagy Volume: 8 Issue: 4 Pages: 445-544
  • DOI: 10.4161/auto.19496
  • Peer Reviewed
• [Journal Article] All members of the EPI64 subfamily of TBC/RabGAPs also have GAP activities toward Ras. (2012)
  • Author(s): Nagai, H., Yasuda, S., Ohba, Y., Fukuda, M. and Nakamura, T.
  • Journal Title: J. Biochem. Volume: 153 Pages: 283-288
  • Peer Reviewed
• [Presentation] 低分子量G蛋白質Rabが制御する多彩な生命現象～メラニン輸送、神経回路網形成、オートファジーから感染症まで～ (2014)
  • Author(s): 福田光則
  • Organizer: 国立感染症研究所・学友会・文化祭シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2014-11-28
  • Invited
• [Presentation] Rabファミリーによるメラニン合成酵素の輸送制御とその破綻による白皮症 (2014)
  • Author(s): 福田光則
  • Organizer: 第86回日本生化学会大会シンポジウム「メンブレントラフィック：基礎と疾患の理解へ向けて」
  • Place of Presentation: 京都
  • Year and Date: 2014-10-18
  • Invited
• [Presentation] The molecular mechanism of melanosome transport in melanocytes. (2014)
  • Author(s): Mitsunori Fukuda
  • Organizer: The SFB629 symposium “Molecular Cell Dynamics”
  • Place of Presentation: 京都
  • Year and Date: 2014-06-13
  • Invited
• [Presentation] 腎臓尿細管上皮細胞におけるRab27依存的及び非依存的Slp2-aの機能 (2014)
  • Author(s): 福田光則
  • Organizer: 第66回日本細胞生物学会大会シンポジウム「細胞の恒常性維持の破綻そして疾患」
  • Place of Presentation: 奈良
  • Year and Date: 2014-06-12
  • Invited
• [Presentation] Atg12-5/16L1複合体によるRab33B依存的膜輸送制御の可能性について (2012)
  • Author(s): 伊藤敬、藤田尚信、齊藤達哉、小松雅明、審良静男、吉森保、福田光則
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-13
• [Presentation] 低分子量GTPase Rabが司る多彩な生命現象 (2012)
  • Author(s): 福田光則
  • Organizer: 理化学研究所・細胞システムコロキウム
  • Place of Presentation: 埼玉
  • Year and Date: 2012-12-07
• [Presentation] リサイクリングエンドソームRabによる神経突起伸長・分化の制御メカニズム
  • Author(s): 福田光則
  • Organizer: 第86回日本生化学会大会シンポジウム「細胞が持つリサイクルシステム研究の新展開」
  • Place of Presentation: 横浜
  • Invited
• [Presentation] メラノソームのロジスティクスを司る低分子量G蛋白質Rabの機能解析
  • Author(s): 福田光則
  • Organizer: 新学術領域研究「細胞内ロジスティクス」・シンポジウム
  • Place of Presentation: 淡路島
  • Invited
• [Remarks] 東北大学大学院生命科学研究科膜輸送機構解析分野
  • URL: http://www.lifesci.tohoku.ac.jp/teacher/t_fukuda/
• [Remarks] 東北大学大学院生命科学研究科膜輸送機構解析分野
  • URL: http://www.lifesci.tohoku.ac.jp/teacher/t_fukuda/