Mechanisms of cell cycle-dependent conversion of the mother centriole to the basal body

2013 Fiscal Year Final Research Report

• Project/Area Number: 24657126
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: MIZUNO Kensaku 東北大学, 生命科学研究科, 教授 (70128396)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 一次繊毛 / 中心体 / 細胞周期 / 基底小体 / NDR / Rabin8 / Rab8 / 小胞輸送

Research Abstract

Primary cilia are formed by conversion of the mother centriole to the basal body. Ciliary membranes are generated by fusion of vesicles to the pericentrosome, a process requiring Rab11-mediated recruitment of Rabin8, Rab8 activation and Rabin8 binding to Sec15, a component of the exocyst.This study showed that NDR2 phosphorylates Rabin8 at Ser-272 and defects in this phosphorylation impair preciliary membrane assembly and ciliogenesis, resulting in accumulation of Rabin8/Rab11-containing vesicles at the pericentrosome. Rabin8 binds to and colocalizes with GTP-bound Rab11 and phosphatidylserine (PS) on pericentrosomal vesicles. The phospho-mimetic S272E mutation of Rabin8 decreases affinity for PS but increases affinity for Sec15. These results suggest that NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by triggering the switch in binding specificity of Rabin8 from PS to Sec15, thereby promoting local activation of Rab8 and ciliary membrane formation.

Research Products

• [Journal Article] Multifaceted roles of Furry proteins in invertebrates and vertebrates (2014)
  • Author(s): Nagai, T., and Mizuno, K.
  • Journal Title: J. Biochem Volume: 155巻 Pages: 137-146
  • Peer Reviewed
• [Journal Article] Furry promotes acetylation of microtubules in the mitotic spindle by inhibition of SIRT2 tubulin deacetylase (2013)
  • Author(s): Nagai, T., Ikeda, M., Chiba, S., Kanno, S., and Mizuno, K.
  • Journal Title: J. Cell Sci Volume: 126巻 Pages: 4369-4380
  • Peer Reviewed
• [Journal Article] NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15 (2013)
  • Author(s): Chiba, S., Amagai, Y., Homma, Y., Fukuda, M., and Mizuno, K
  • Journal Title: EMBO J Volume: 32巻 Pages: 874-855
  • Peer Reviewed
• [Journal Article] Cancer susceptibility and embryonic lethality in Mob1A/1B double mutant mice (2012)
  • Author(s): Nishio, M., Hamada, K., Kawahara, K., Sasaki, M., Noguchi, F., Chiba, S., Mizuno, K., Suzuki, S. O., Dong, Y., Tokuda, M., Morikawa, T., Hikasa, H., Eggenschwiler, J., Yabuta, N., Nojima, H., Nakagawa, K., Hata, Y., Nishina, H., Mimori, K., Mori, M., Sasaki, T., Mak, T. W., Nakano, T., Itami, S., and Suzuki, A.
  • Journal Title: J. Clin. Inv Volume: 122巻 Pages: 4505-4518
  • Peer Reviewed
• [Journal Article] Furry protein promotes Aurora A-mediated Polo-like kinase 1 activation (2012)
  • Author(s): Ikeda, M., Chiba, S., Ohashi, K., and Mizuno, K.
  • Journal Title: J. Biol. Chem Volume: 287巻 Pages: 3707-3721
  • Peer Reviewed
• [Presentation] NDRによるPI4KIIIßのリン酸化と一次繊毛形成における機能 (2013)
  • Author(s): 清水祐子、高橋克宣、水野健作
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 20131203-06
• [Presentation] Furryによるチューブリン脱アセチル化酵素SIRT2の活性制御と分裂期紡錘体微小管のアセチル化に対する役割 (2013)
  • Author(s): 永井友朗、池田真教、千葉秀平、菅野新一郎、水野健作
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸
  • Year and Date: 20131203-06
• [Presentation] NDR2によるRabin8のリン酸化と一次繊毛形成における機能 (2013)
  • Author(s): 千葉秀平、天貝佑太、本間悠太、福田光則、水野健作
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 20130911-13
• [Presentation] NDR2-mediated Rabin8 phosphorylation is crucial for ciliogenesis by switching binding specificity from phosphatidylserine to Sec15 (2013)
  • Author(s): Chiba,S., Amagai,Y., Homma,Y., Fukuda,M., Mizuno,K.
  • Organizer: FASEB Science Research Conferences Biology of Cilia & Flagella
  • Place of Presentation: Niagara Falls, New York, USA
  • Year and Date: 20130623-28
• [Presentation] Furry promotes acetylation of microtubules in the mitotic spindle via inhibition of SIRT2 tubulin deacetylase (2013)
  • Author(s): Tomoaki Nagai, Shuhei Chiba, Masanori Ikeda, Shin-ichiro Kanno, Kensaku Mizuno
  • Organizer: 第65回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 20130619-21
• [Presentation] NDR2-mediated Rabin8 Phosphorylation is Crucial for Ciliogenesis by Switching Binding Specificity from Phosphatidylserine to Sec15 (2013)
  • Author(s): Chiba, S., Mizuno, K.
  • Organizer: 第25回CDBミーティング
  • Place of Presentation: 神戸
  • Year and Date: 20130617-18
• [Presentation] NDR2によるRabin8のリン酸化と一次繊毛形成における機能 (2013)
  • Author(s): 千葉秀平、天貝佑太、本間悠太、福田光則、水野健作
  • Organizer: 日本生化学会東北支部第79回例会・シンポジウム
  • Place of Presentation: 仙台
  • Year and Date: 2013-05-11
• [Presentation] 一次繊毛形成における膜輸送制御 : 繊毛病との関連 (2013)
  • Author(s): 水野健作、千葉秀平
  • Organizer: 東北大学GCOEシンポジウム「Network Medicineによる医学・生命科学の新たな潮流」
  • Place of Presentation: 仙台
  • Year and Date: 2013-02-01
• [Presentation] Furry is a positive regulator of microtubule acetylation in mitotic spindle (2012)
  • Author(s): T. Nagai, S. Chiba, M. Ikeda, S-I. Kanno, A.Yasui, K. Ohashi, K. Mizuno
  • Organizer: 第52回American Society for Cell Biology Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20121213-20
• [Book] 一次繊毛形成と細胞周期のクロストーク, 実験医学増刊「細胞周期による高次生命現象の制御と疾患」 (2013)
  • Author(s): 千葉秀平、天貝佑太、水野健作
  • Total Pages: 252-256
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/