Study on the cellular logistics of lysosome-related organelles and their related diseases

2012 Fiscal Year Final Research Report

• Project Area: Intracellular logistics: interdisciplinary approaches to pathophysiology of membrane traffic
• Project/Area Number: 20113006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: FUKUDA Mitsunori 東北大学, 大学院・生命科学研究科, 教授 (50311361)
• Project Period (FY): 2008 – 2012
• Keywords: Rab / メラノソーム / リソソーム / スクリーニング / 膜輸送

Research Abstract

Defects in formation and transport of lysosome-related organelles (LROs) have been shown to cause human hereditary diseases, but the molecular mechanisms of their intracellular dynamics are poorly understood. In this study, we used melanosomes as a model for LROs and investigated their dynamics at the molecular level. We succeeded in identifying novel regulators that play a key role in melanosome biogenesis, matUration, and/or transport in melanocytes.

Research Products

• [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)
  • DOI: Doi:10.1038/jid.2013.156
  • Peer Reviewed
• [Journal Article] Rab 12 regulates mTORC1 activity and autophagy through controlling the degradation of amino-acid transporter PAT4 (2013)
  • Author(s): Matsui, T & Fukuda M
  • Journal Title: EMBO Rep Volume: 14 Pages: 450-457
  • DOI: Doi:10.1038/embor.2013.32
  • Peer Reviewed
• [Journal Article] Essential role of RAB27A in determining constitutive human skin color (2012)
  • Author(s): Yoshida-Amano, Y, Hachiya, A., Ohuchi, A., Kobinger, G P, Kitahara, T., Takema, Y & Fukuda, M
  • Journal Title: PLoS One Volume: 7 Pages: e41160
  • DOI: Doi:10.1371/j ournal.pone.0041160
  • Peer Reviewed
• [Journal Article] Synaptotagmin-like proteins control the formation of an single apical membrane domain in epithelial cells (2012)
  • Author(s): Galvez-Santisteban, M., Rodriguez-Fraticelli, A.E, Bryant, D. M., Vergarajauregui, S., Yasuda, T., Banon-Rodriguez,1., Bemascone, I.,Datta, A., Spivak, N., Young, K., Slim, C. L, Brakeman, P. R, Fukuda. M., Mostov, K. E. & Martin-Belmonte, F
  • Journal Title: Nature Cell-Biol Volume: 14 Pages: 838-849
  • DOI: Doi:10.1038/ncb2541
  • Peer Reviewed
• [Journal Article] The Rab interacting lysosomal protein (RILP)homology domain functions as a novel effector domain for small GTPase Rab36: Rab36 regulates retrograde melanosome transport in melanocytes (2012)
  • Author(s): Matsui, T., Ohbayashi, N .& Fukuda, M
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 28619-28631
  • DOI: Doi:10.1074/jbc.M112.370544
  • 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., Saegusa, C., Kamakura, S., Sumimoto, H. & Fukuda. M
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 3229-3239
  • DOI: Doi:10.1091/mbcE12-02-0104
  • 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 Pages: 3193-3202
  • DOI: Doi:10.1091/mbc.E12-01-0010
  • Peer Reviewed
• [Journal Article] Role of Rab family GTPases and their effectors in melanosomal logistics (2012)
  • Author(s): Ohbayashi, N. & Fukuda. M
  • Journal Title: J. Biochem Volume: 151 Pages: 343-351
  • DOI: Doi:10.1093/jb/mvs009
  • Peer Reviewed
• [Journal Article] Functional involvement of Rab1A in microtubule-dependent anterograde melanosome transport in melanocytes (2012)
  • Author(s): Ishida, M., Ohbayashi, N., Mamta, Y, Ebata, Y & Fukuda. M
  • Journal Title: J. Cell. Sci Volume: 125 Pages: 5177-5187
  • DOI: Doi:10.1242/jcs.109314
  • Peer Reviewed
• [Journal Article] Small GTPase Rab17 regulates dendritic morphogenesis and postsynaptic development of hippocampal neurons (2012)
  • Author(s): Mori, Y, Matsui, T., Fumtani, Y, Yoshihara, Y & Fukuda. M
  • Journal Title: J. Biol. Chem Volume: 287 Pages: 8963-8973
  • DOI: Doi:10.1074/jbc.M111.314385
  • Peer Reviewed
• [Journal Article] Rab35 regulates Arf6 activity through centaurin-β2 (ACAP2)during neurite outgrowth (2012)
  • Author(s): Kobayashi, H. & Fukuda. M
  • Journal Title: J. Cell. Sci Volume: 125 Pages: 2235-2243
  • DOI: Doi:10.1242/jcs.098657
  • Peer Reviewed
• [Journal Article] An ARF6/Rab35 GTPase cascade for endocytic recycling and successful cytokinesis (2012)
  • Author(s): Chesneau, L, Dambournet, D., Machicoane, M., Kouranti, I., Fukuda, M., Goud, G & Echard, A
  • Journal Title: Curr. Biol Volume: 24 Pages: 147-153
  • DOI: Doi:10.1016/j.cub.2011.11.058
  • Peer Reviewed
• [Journal Article] The Rab21-GEF activity of Varp, but not its Rab32/38 effector function, is required for dendrite formation in melanocytes (2012)
  • Author(s): Ohbayashi, N., Yatsu, A., Tamura, K. & Fukuda, M
  • Journal Title: Mol. Biol. Cell Volume: 23 Pages: 669-678
  • DOI: Doi:10.1091/mbcE11-04-0324
  • Peer Reviewed
• [Journal Article] Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p 150Glued complex (2012)
  • Author(s): Ohbayashi, N., Maruta, Y, Ishida, M .& Fukuda, M
  • Journal Title: J. Cell. Sci Volume: 125 Pages: 1508-1518
  • DOI: Doi:10.1242/jcs.094185
  • Peer Reviewed
• [Journal Article] Atg16L2, a novel isoform of mammalian Atg16L that is not essential for canonical autophagy despite forming an At12-5-16L2 complex (2011)
  • Author(s): Ishibashi, K., Fujita, N., Kanno, E., Omori, H.,Yoshimori, T., Itoh, T .& Fukuda. M
  • Journal Title: Autophagy Volume: 7 Pages: 1500-1513
  • DOI: Doi:10.4161/auto.7.12.18025
  • Peer Reviewed
• [Journal Article] EPI64 protein functions as a physiological GTPase-activating protein for Rab27 protein and regulates amylase release in rat parotid acinar cells (2011)
  • Author(s): Imai, A., Yoshie, S., Ishibashi, K., Haga-TsTsujimura, M., Nashida, T., Shimomura, H. & Fukuda, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 33854-33862
  • DOI: Doi:10.1074/jbc.M111281394
  • Peer Reviewed
• [Journal Article] Small GTPase Rab12 regulates transferrin receptor degradation: Implications for a novel membrane trafficking pathway from recycling endosomes to lysosomes (2011)
  • Author(s): Matsui, T. & Fukuda, M
  • Journal Title: Cell. Logistics Volume: 1 Pages: 155-158
  • DOI: Doi:10.4161/cl.1.4.18152
  • Peer Reviewed
• [Journal Article] Small GTPase Rab12 regulates constitutive degradation of transferrin receptor (2011)
  • Author(s): Matsui, T., Itoh, T. & Fukuda, M
  • Journal Title: Traffic Volume: 12 Pages: 1432-1443
  • DOI: Doi:10.1111/j.1600-0854.2011
  • Peer Reviewed
• [Journal Article] Genome-wide investigation of the Rab binding activity of RUN domains:Development of a novel tool that specifically traps GTP-Rab35 (2011)
  • Author(s): Fukuda, M., Kobayashi, H., Ishibashi, K.& Ohbayashi, N
  • Journal Title: Cell Struct Funct Volume: 36 Pages: 155-170
  • DOI: Doi:10.1247/csf.11001
  • Peer Reviewed
• [Journal Article] OATLI, a novel autophagosome-resident Rab33B-GAP, regulates autophagosomal maturation (2011)
  • Author(s): Itoh, T., Kanno, E., Uemura, T., Waguri, S. & Fukuda, M
  • Journal Title: J. Cell Boil Volume: 192 Pages: 839-853
  • DOI: Doi:10.1083/jcb.201008107
  • Peer Reviewed
• [Journal Article] Structure-function analysis of VP S9-ankyrin-repeat protein(Varp)in the trafficking of tyrosinase-related protein 1 in melanocytes (2011)
  • Author(s): Tamura, K., Ohbayashi, N., Ishibashi, K. & Fukuda, M
  • Journal Title: J. Boil. Chem Volume: 286 Pages: 7507-7521
  • DOI: Doi:10.1074/jbc.M110.191205
  • Peer Reviewed
• [Journal Article] Function al characterization of two RAB2 7A missense mutations found in Griscelli syndrome type 2 (2010)
  • Author(s): Ohbayashi, N, Mamishi, S., Ishibashi, K., Maruta, Y, Pourakbari, B., Tamizifar, B., Mohammadpour, M., Fukuda. M. & Parvaneh, N
  • Journal Title: Pigment Cell Melanoma Res Volume: 23 Pages: 365-374
  • DOI: Doi:10.1111/j-1755-148×2010.00705.x
  • Peer Reviewed
• [Journal Article] Comprehensive screening for novel Rab-binding proteins by GST pull-down assay using 60 different mammalian Rabs (2010)
  • Author(s): Kanno, E., Ishibashi, K., Kobayashi, H., Matsui, T., Ohbayashi, N. & Fukuda, M
  • Journal Title: Traffic Volume: 11 Pages: 491-507
  • DOI: Doi:10.1111/j.1600-0854.2010.01038.x
  • Peer Reviewed
• [Journal Article] Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein-1 (BICDR-1) regulates neuritogenesis (2010)
  • Author(s): Schlager, M. A., Kapitein, L. C., Grigoriev, I., Burzynski, G M., Wulf, P. S., Keijzer, N., de Graaff, E, Fukuda. M, Shepherd, I. T., Akhmanova, A. & Hoogenraad, C.C.
  • Journal Title: EMBO J Volume: 29 Pages: 1637-1651
  • DOI: Doi:10.1038/emboj.2010.51
  • Peer Reviewed
• [Journal Article] Broad-minded links cell cycle-related kinase to cilia assembly and hedgehog signal transduction (2010)
  • Author(s): Ko, H. W., Norman, R. X., Tran, J., Fuller, K. P.,Fukuda, M. & Eggenschwiler, J. T
  • Journal Title: Dev. Cell Volume: 8 Pages: 237-247
  • DOI: Doi:10.1016/j.devcel.2009.12.014
  • Peer Reviewed
• [Journal Article] Rab27a and Rab27b control different steps of the exosome secretion pathway (2010)
  • Author(s): Ostrowski, M, Carmo, N. B., Krumeich, S., Fanget, I., Raposo, G, Savina, A., Moita, C. F. Schauer, K., Hume, A. N., Freitas, R. P., Goud B., Benaroch, P., Hacohen, N., Fukuda, M, Desnos, C., Seabra, M. C., Darchen, E, Amigorena, S., Moita, L. F. & Thery, C
  • Journal Title: Nature Cell Biol Volume: 12 Pages: 19-30
  • DOI: Doi:10.1038/ncb2000
  • Peer Reviewed
• [Journal Article] Varp is a novel Rab32/38-binding protein that regulates Tyrpl trafficking in melanocytes (2009)
  • Author(s): Tamura, K., Ohbayashi, N., Maruta, Y, Kanno, E, Itoh, T. & Fukuda. M
  • Journal Title: Mol. Biol. Cell Volume: 20 Pages: 2900-2908
  • DOI: Doi:10.1091/mbcE08-12-1161
  • Peer Reviewed
• [Journal Article] Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity (2009)
  • Author(s): Ishibashi, K., Kanno, E, Itoh, T. & Fukuda, M
  • Journal Title: Ganes Cells Volume: 14 Pages: 41-52
  • DOI: Doi:10.1111/j.1365-2443.2008.01251.x
  • Peer Reviewed
• [Journal Article] Role of Rab27 in synaptic transmission at the squid giant synapse (2008)
  • Author(s): Yu, E, Kanno, E, Choi, S., Sugimori, M., Moreira, J. E., Llinas, R. R. & Fukuda. M
  • Journal Title: Proc. Nat. Acad. Sci. USA Volume: 105 Pages: 16003-16008
  • DOI: Doi:10.1073/pnas.0804825105
  • Peer Reviewed
• [Journal Article] Structural basis for the exclusive specificity of Slac2-a/melanophilin for the Rab27 GTPases (2008)
  • Author(s): Kukimoto-Niino, M., Sakamoto, A., Kanno, E.,Hanawa-Suetsugu, K., Terada, T., Shirouzu, M., Fukuda. M. & Yokoyama, S
  • Journal Title: Structure Volume: 16 Pages: 1478-1490
  • DOI: Doi:10.1016/j.str2008.07.014
  • Peer Reviewed
• [Journal Article] Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates autophagosome formation (2008)
  • Author(s): Itoh, T., Fujita, N., Kanno, E., Yamamoto, A., Yoshimori, T. & Fukuda. M
  • Journal Title: Mol. Biol. Cell Volume: 19 Pages: 2916-2925
  • DOI: Doi:10.1091/mbc.E07-12-1231
  • Peer Reviewed
• [Journal Article] The Atg16L complex specifies the site of LC31ipidation for membrane biogenesis in autophagy (2008)
  • Author(s): Fujita, N., Itoh, T., Omori, H., Fukuda, M., Noda, T. & Yoshimori, T
  • Journal Title: Mol. Biol. Cell Volume: 19 Pages: 2092-2100
  • DOI: Doi:10.1091/mbc.E07-12-1257
  • Peer Reviewed
• [Journal Article] Large scale screening for novel Rab effectors reveals unexpected broad Rab binding specificity (2008)
  • Author(s): Fukuda, M., Kanno, E., Ishibashi, K. & Itoh, T
  • Journal Title: Mol. Cell. Proteomics Volume: 7 Pages: 1031-1042
  • DOI: Doi:10.1074/mcp.M700569-MCP200
  • Peer Reviewed
• [Journal Article] Regulation of secretory vesicle traffic by Rab small GTPases (2008)
  • Author(s): Fukuda. M
  • Journal Title: Mol. Life Sci Volume: 65 Pages: 2801-2813
  • DOI: Doi:10.1007/s00018-008-8351-4
  • Peer Reviewed
• [Presentation] 低分子量GTPase Rabが司る多彩な生命現象～メラニン輸送、神経細胞の極性輸送からオートファジーまで～ (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] メラノソームの微小管輸送における低分子量Gタンパク質Rabの役割 (2012)
  • Author(s): 福田光則
  • Organizer: 第24回日本色素細胞学会学術大会ワークショップ
  • Place of Presentation: 長浜
  • Year and Date: 2012-11-24
• [Presentation] 分子レベルで見たメラニン炬素の動く仕組み (2012)
  • Author(s): 福田光則
  • Organizer: 日本放射線影響学会角55回大会ワークショップ「紫外線に対する生物応答:細胞から皮膚まで」
  • Place of Presentation: 仙台
  • Year and Date: 2012-09-06
• [Presentation] メラノソームをモデル系とした細胞内小胞輸送機構の解明 (2011)
  • Author(s): 福田光則
  • Organizer: ワークこヨップ・量子ビームを用いた物質・生命化学の新展開
  • Place of Presentation: 仙台
  • Year and Date: 2011-12-20
• [Presentation] Rabの網羅的解析ツールを用いた新規膜輸送経路の探索と新たなRa機能の同定 (2011)
  • Author(s): 福田光則
  • Organizer: 第84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研究の最近のトレンド(低分子量GTPaseによる多彩な制御機構)」
  • Place of Presentation: 京都
  • Year and Date: 2011-09-24
• [Presentation] メラニン輸送の分子メカニズム解明とその応用 (2010)
  • Author(s): 福田光則
  • Organizer: 第35回日本香粧品学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2010-06-04
• [Presentation] Rab small GTPase control melanosome formation and transpot in melanocytes (2010)
  • Author(s): Mitsunori Fukuda
  • Organizer: The 1st UCL-Tohoku University Symposium
  • Place of Presentation: London, UK
  • Year and Date: 2010-03-15
• [Presentation] オートファジー制御に関与する低分子量GTPase Rabの機能解析 (2009)
  • Author(s): 福田光則
  • Organizer: 第82回日本生化学会大会シンポジウム「低分子量GTPaseから眺めるメンブレントラフック研究の新展開」
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] Atg16L1 is a potential effector for small GTPase Rab33 that modulates autophagosome formation (2009)
  • Author(s): Mitsunori Fukuda
  • Organizer: 5th Intemational Symposium on Autophag
  • Place of Presentation: Otsu
  • Year and Date: 2009-09-25
• [Presentation] メラノソーム形成・成熟画送におけるRabシグナリングネットワークの解析 (2009)
  • Author(s): 福田光則
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会シンポジウム「毛包形成とメラノサイト分化のメカニズム」
  • Place of Presentation: 神戸
  • Year and Date: 2009-09-25
• [Book] Rab27による分泌小胞の輸送制御メカニズム",ブレインサイエンスレビュー2008 (2008)
  • Author(s): 福田光則
  • Total Pages: 2008
  • Publisher: ブレインサイエンス振興財団
• [Remarks]
  • URL: http://www. lifesci.tohoku.ac.jp/teacher/t_fukuda/
• [Patent(Industrial Property Rights)] Rab27A不活性化剤 (2011)
  • Inventor(s): 福田光則、伊藤敬
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 特許、4869685
  • Acquisition Date: 2011-11-25
• [Patent(Industrial Property Rights)] Slac2-aタンパク質量低減剤、myosin Va タンパク質量低減剤、及びSlp2-aタンパク質量低減剤 (2009)
  • Inventor(s): 畑友紀、高山明美、近藤千春、板倉研、福田光則
  • Industrial Property Rights Holder: 株式会社コーセー
  • Industrial Property Number: 特許、特願2009-294615
  • Filing Date: 2009-12-25
• [Patent(Industrial Property Rights)] Slp-2aタンパク質低減剤、及びミオシンー5aタンパク質低減剤 (2009)
  • Inventor(s): 板倉研、高山明美、近藤千春、福田光則
  • Industrial Property Rights Holder: 株式会社コーセー
  • Industrial Property Number: 特許、特願2009-075485
  • Filing Date: 2009-03-26
• [Patent(Industrial Property Rights)] メラノソーム輸送阻害剤、及び皮膚外用剤 (2008)
  • Inventor(s): 板倉研、畑友紀、成英次、高山明美、福田光則
  • Industrial Property Rights Holder: 株式会社コーセー
  • Industrial Property Number: 特許、特願2008-56389
  • Filing Date: 2008-03-06