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シリア形成における小胞輸送と脂質代謝の協調作用機構の解明

Publicly Offered Research

Project AreaCilium-centrosome system regulating biosignal flows
Project/Area Number 15H01198
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

福田 光則  東北大学, 生命科学研究科, 教授 (50311361)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords低分子量G蛋白質Rab / シリア / 膜輸送 / Rab panel / スクリーニング / hTERT-RPE1細胞 / Rabエフェクター / 脂質代謝 / 繊毛関連疾患
Outline of Annual Research Achievements

一次繊毛(シリア)は外界からの刺激に対するセンサーとして働き、様々なシグナル受容に必須の役割を果たすため、シリア形成の異常は種々の繊毛関連疾患を引き起こす。近年これらの疾患の原因遺伝子が同定され、シリアを構成する基本的な分子群の存在が明らかになって来た。興味深いことに、これらの分子の中には膜輸送の制御因子である低分子量G蛋白質RabやArfが含まれており、シリア形成における膜(小胞)輸送の重要性が注目を集めている。しかし、シリア形成時におけるゴルジ体から基底小体への繊毛小胞の輸送、あるいはシリアへの膜蛋白質や脂質膜の供給の詳細な分子機構は未だ十分に解明されていない。そこで本研究では、当研究室で独自に開発してきた全ての哺乳類Rab分子を網羅的に解析するツール(Rab panel)を駆使して、シリア形成に関与するRab分子の網羅的な機能解析に取り組んだ。昨年度に引き続き、本年度もhTERT-RPE1細胞のシリア形成をモデル系として、特異的なsiRNAを用いた網羅的なRabのノックダウンスクリーニングを行い、これまでに報告のあるRab10、Rab11以外にシリア形成に関与する複数の新規Rab分子の同定に成功した。次に、CRISPR/Cas9のゲノム編集技術を用いてこれらの候補Rab分子のノックアウト細胞株を作製したところ、一部のノックアウト細胞でシリアの形成が顕著に阻害されていることが確認できた。さらに、これらのRab分子がどのような膜輸送機構を制御することにより、シリア形成を促進しているのかを明らかにするため、これらのRabに対する特異的なエフェクター分子を酵母two-hybrid法により探索した。その結果、候補Rabとシリア近傍で共局在を示すエフェクター分子を得ることにも成功した。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (40 results)

All 2017 2016 2015 Other

All Int'l Joint Research (4 results) Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 17 results,  Acknowledgement Compliant: 11 results,  Open Access: 5 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 11 results) Remarks (1 results)

  • [Int'l Joint Research] New York University School of Medicine(米国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] University of Oxford/University of Leeds(英国)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Universidad de Chile(Chile)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] Tel Aviv University(Israel)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Cdk5 regulation of the GRAB-mediated Rab8-Rab11 cascade in axon outgrowth.2017

    • Author(s)
      Furusawa, K., Asada, A., Urrutia, P., Gonzalez-Billault, C., Fukuda, M. and Hisanaga, S. I.
    • Journal Title

      J. Neurosci.

      Volume: 37 Issue: 4 Pages: 790-806

    • DOI

      10.1523/jneurosci.2197-16.2017

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] M-INK, a novel tool for visualizing melanosomes and melanocores.2017

    • Author(s)
      Ishida, M., Marubashi, S. and Fukuda, M.
    • Journal Title

      J. Biochem.

      Volume: 161 Pages: 323-326

    • DOI

      10.1093/jb/mvw100

    • NAID

      40021219775

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia.2017

    • Author(s)
      Aoki, Y., Manzano, R., Lee, Y., Dafinca, R., Aoki, M., Douglas, A. G. L., Varela, M. A., Sathyaprakash, C., Scaber, J., Barbagallo, P., Vader, P., Mager, I., Ezzat, K., Turner, M. R., Ito, N., Gasco, S., Ohbayashi, N., El-Andaloussi, S., Takeda, S., Fukuda, M., Talbot, K. and Wood, M. J. A.
    • Journal Title

      Brain

      Volume: 140 Issue: 4 Pages: 887-897

    • DOI

      10.1093/brain/awx024

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of podocalyxin trafficking by Rab small GTPases in 2D and 3D epithelial cell cultures.2016

    • Author(s)
      Mrozowska, P. S. and Fukuda, M.
    • Journal Title

      J. Cell Biol.

      Volume: 213 Issue: 3 Pages: 355-369

    • DOI

      10.1083/jcb.201512024

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A Varp-binding protein, RACK1, regulates dendrite outgrowth through stabilization of Varp protein in mouse melanocytes.2016

    • Author(s)
      Marubashi, S., Ohbayashi, N. and Fukuda, M.
    • Journal Title

      J. Invest. Dermatol.

      Volume: 136 Issue: 8 Pages: 1672-1680

    • DOI

      10.1016/j.jid.2016.03.034

    • NAID

      120007129451

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells.2016

    • Author(s)
      Wankel, B., Ouyang, J., Guo, X., Hadjiolova, K., Miller, J., Liao, Y., Tham, D. K. L., Romih, R., Andrade, L. R., Gumper, I., Simon, J.-P., Sachdeva, R., Tolmachova, T., Seabra, M. C., Fukuda, M., Schaeren-Wiemers, N., Hong, W. J., Sabatini, D. D., Wu, X.-R., Kong, X., Kreibich, G., Rindler, M. J. and Sun T.-T.
    • Journal Title

      Mol. Biol. Cell

      Volume: 27 Issue: 10 Pages: 1621-1634

    • DOI

      10.1091/mbc.e15-04-0230

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Rabin8 regulates neurite outgrowth in both GEF-activity-dependent and -independent manners.2016

    • Author(s)
      Homma, Y. and Fukuda, M.
    • Journal Title

      Mol. Biol. Cell

      Volume: 27 Issue: 13 Pages: 2107-2118

    • DOI

      10.1091/mbc.e16-02-0091

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rab35 functions in axon elongation are regulated by p53-related protein kinase (PRPK) in a mechanism that involves Rab35 protein degradation and the microtubule-associated protein 1B.2016

    • Author(s)
      Villarroel-Campos, D., Henriquez, D. R., Bodaleo, F. J., Oguchi, M. E., Bronfman, F. C., Fukuda, M. and Gonzalez-Billault, C.
    • Journal Title

      J. Neurosci.

      Volume: 36 Issue: 27 Pages: 7298-7313

    • DOI

      10.1523/jneurosci.4064-15.2016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Release of infectious hepatitis C virus from Huh7 cells occurs via a trans-Golgi network to endosome pathway independent of very-low-density lipoprotein secretion.2016

    • Author(s)
      Mankouri, J., Walter, C., Stewart, H., Bentham, M. J., Park, W. S., Heo, W. D., Fukuda, M., Griffin, S. and Harris, M.
    • Journal Title

      J. Virol.

      Volume: 90 Issue: 16 Pages: 7159-7170

    • DOI

      10.1128/jvi.00826-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Multiple roles of VARP in endosomal trafficking: Rabs, retromer components and R-SNARE VAMP7 meet on VARP.2016

    • Author(s)
      Fukuda, M.
    • Journal Title

      Traffic

      Volume: 17 Issue: 7 Pages: 709-719

    • DOI

      10.1111/tra.12406

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Multiple types of guanine nucleotide exchange factors (GEFs) for Rab small GTPases.2016

    • Author(s)
      Ishida, M., Oguchi, M. E. and Fukuda, M.
    • Journal Title

      Cell Struct. Funct.

      Volume: 41 Issue: 2 Pages: 61-79

    • DOI

      10.1247/csf.16008

    • NAID

      130005163247

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells.2016

    • Author(s)
      Mrozowska, P. S. and Fukuda, M.
    • Journal Title

      Small GTPases

      Volume: 7 Issue: 4 Pages: 231-238

    • DOI

      10.1080/21541248.2016.1211068

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] RUTBC1 functions as a GTPase-activating protein for Rab32/38 and regulates melanogenic enzyme trafficking in melanocytes.2016

    • Author(s)
      Marubashi, S., Shimada, H., Fukuda, M. and Ohbayashi, N.
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 3 Pages: 1427-1440

    • DOI

      10.1074/jbc.m115.684043

    • NAID

      120007128493

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Rab12 regulates retrograde transport of mast cell secretory granules by interacting with the RILP-dynein complex.2016

    • Author(s)
      Efergan, A., Azouz, N. P., Klein, O., Noguchi, K., Rothenberg, M. E., Fukuda, M. and Sagi-Eisenberg, R.
    • Journal Title

      J. Immunol.

      Volume: 196 Issue: 3 Pages: 1091-1101

    • DOI

      10.4049/jimmunol.1500731

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Lysosome-related organelles.2016

    • Author(s)
      Fukuda M.
    • Journal Title

      Encyclopedia of Cell Biology (Bradshaw R. A. and Stahl P. D ed.)

      Volume: 2 Pages: 235-242

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small GTPase Rab2B and its specific binding protein Golgi-associated Rab2B interactor-like 4 (GARI-L4) regulate Golgi morphology.2015

    • Author(s)
      Aizawa, M. and Fukuda, M.
    • Journal Title

      J. Biol. Chem.

      Volume: 290 Issue: 36 Pages: 22250-22261

    • DOI

      10.1074/jbc.m115.669242

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Functional analysis of Rab27A and its effector Slp2-a in renal epithelial cells.2015

    • Author(s)
      Yasuda, T., Mrozowska, P. S. and Fukuda, M.
    • Journal Title

      Methods Mol. Biol.

      Volume: 1298 Pages: 127-139

    • DOI

      10.1007/978-1-4939-2569-8_11

    • ISBN
      9781493925681, 9781493925698
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] 低分子量G蛋白質Rabによるエンドソーム輸送の制御機構2017

    • Author(s)
      福田光則
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県・長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Roles of Rab family small GTPases in polarized trafficking in epithelial cells.2017

    • Author(s)
      Mitsunori Fukuda
    • Organizer
      The 2017 Japan-NIH joint Symposium on Advances in Biomedical Research and Disease
    • Place of Presentation
      Sendai (Japan)
    • Year and Date
      2017-02-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Roles of Rab small GTPases in membrane traffic: molecular mechanisms of melanosome transport in melanocytes.2016

    • Author(s)
      福田光則
    • Organizer
      日本研究皮膚科学会 第41回年次学術大会・総会・招待講演
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-12-10
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Rab GTPaseによる多彩なメンブレントラフィックの制御機構2016

    • Author(s)
      福田光則
    • Organizer
      OLYMPUS Innovation Forum 2016
    • Place of Presentation
      横浜ベイホテル東急(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] メラノソームを染色する新規ツールの開発2016

    • Author(s)
      石田森衛、丸橋総史郎、福田光則
    • Organizer
      第27回日本色素細胞学会学術大会・ワークショップ「メラノソームの動態に挑む」
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜県・岐阜市)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
  • [Presentation] Rab small GTPases regulate polarized trafficking in epithelial cells.2016

    • Author(s)
      Mitsunori Fukuda
    • Organizer
      Ireland - Japan Joint Seminar: Membrane Trafficking, Cilia and Oxygen Sensing
    • Place of Presentation
      Tokyo (Japan)
    • Year and Date
      2016-10-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 細胞外環境に依存したRabファミリーによる上皮細胞極性輸送の制御2016

    • Author(s)
      福田光則
    • Organizer
      第89回日本生化学会大会シンポジウム「膜動態を介した細胞間・細胞外環境との相互作用の制御」
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Regulation of podocalyxin trafficking by Rab small GTPases in epithelial cells.2016

    • Author(s)
      Mitsunori Fukuda
    • Organizer
      2016 FASEB Science Research Conference “GTPases in Trafficking, Autophagy and Disease”
    • Place of Presentation
      West Palm Beach, FL (USA)
    • Year and Date
      2016-09-21
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Rab12 regulates podocalyxin exit from early endosomes through tubulation of endosomal membranes.2016

    • Author(s)
      Paulina S. Mrozowska and Mitsunori Fukuda
    • Organizer
      2016 FASEB Science Research Conference “GTPases in Trafficking, Autophagy and Disease”
    • Place of Presentation
      West Palm Beach, FL (USA)
    • Year and Date
      2016-09-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メラノソームの生合成と輸送の分子メカニズム2016

    • Author(s)
      福田光則
    • Organizer
      フジフィルム株式会社 医薬品・ヘルスケア研究所講演会
    • Place of Presentation
      (神奈川県・足柄上郡)
    • Year and Date
      2016-08-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 上皮細胞のポドカリキシン極性輸送におけるRabシグナリングネットワークの解析2016

    • Author(s)
      福田光則
    • Organizer
      第68回日本細胞生物学会大会シンポジウム「高次生命機能を司るメンブレントラフィック:分子基盤からその破綻による疾患発症の理解に向けて」
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 細胞内小胞輸送が制御する多彩な生命現象~メラニン輸送、オートファジー、ヒスタミン分泌まで~2016

    • Author(s)
      福田光則
    • Organizer
      第40回皮膚科免疫セミナー
    • Place of Presentation
      経団連会館(東京都、千代田区)
    • Year and Date
      2016-03-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] The molecular mechanisms of anterograde melanosome transport on microtubules in mammalian melanocytes.2015

    • Author(s)
      Morie Ishida, Norihiko Ohbayashi and Mitsunori Fukuda
    • Organizer
      The 2015 Annual Meeting of the American Society for Cell Biology
    • Place of Presentation
      San Diego, CA, USA
    • Year and Date
      2015-12-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RUTBC1はRab32/38の不活性化を通してメラニン合成酵素の輸送を調節する2015

    • Author(s)
      大林典彦、丸橋総史郎、福田光則
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会ワークショップ「高次生命機能を支えるメンブレントラフィック」
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 新規Varp結合分子・RACK1はVarpの安定化を介してメラノサイトのデンドライト伸長に関与する2015

    • Author(s)
      丸橋総史郎、大林典彦、福田光則
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Rab33Aはラット耳下腺腺房細胞においてβ刺激性アミラーゼ分泌機構に関与している2015

    • Author(s)
      今井あかね、辻村麻衣子、吉江紀夫、福田光則
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県、神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] メラノサイトにおけるメラノソームの微小管順行性輸送メカニズム2015

    • Author(s)
      石田森衛、福田光則
    • Organizer
      第26回日本色素細胞学会学術大会
    • Place of Presentation
      札幌医科大学(北海道、札幌市)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Varpの新規結合分子の探索とメラノサイトのデンドライト形成への関与2015

    • Author(s)
      丸橋総史郎、大林典彦、福田光則
    • Organizer
      日本生化学会東北支部 第81回例会
    • Place of Presentation
      東北大学さくらホール(宮城県、仙台市)
    • Year and Date
      2015-05-09
    • Related Report
      2015 Annual Research Report
  • [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/

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report

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Published: 2015-04-16   Modified: 2022-01-31  

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