Regulatory mechanism of Rab14 and its effector proteins in post-Golgi membrane trafficking

2010 Fiscal Year Final Research Report

• Project/Area Number: 21770203
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Kyoto University
• Principal Investigator: SHIN Hye-Won Kyoto University, 生命科学系キャリアパス形成ユニット, 特定助教 (10345598)
• Project Period (FY): 2009 – 2010
• Keywords: 細胞 / メンブレントラフィック / 小胞輸送 / 低分子量GTPase / エンドソーム

Research Abstract

Here, we report that Rab14 binds in a GTP-dependent manner to RUFY1/Rabip4, which had been originally identified as a Rab4 effector. Rab14 colocalizes well with Rab4 on peripheral endosomes. Depletion of Rab14, but not Rab4, causes dissociation of RUFY1 from endosomal membranes. Coexpression of RUFY1 with either Rab14 or Rab4 induces clustering and enlargement of endosomes, while a RUFY1 mutant lacking the Rab4-binding region does not induce a significant morphological change in the endosomal structures even when coexpressed with Rab14 or Rab4. These findings suggest that Rab14 and Rab4 act sequentially, together with RUFY1 ; Rab14 is required for recruitment of RUFY1 onto endosomal membranes, and subsequent RUFY1 interaction with Rab4 may allow endosomal tethering and fusion. Depletion of Rab14 or RUFY1, as well as Rab4, inhibits efficient recycling of endocytosed transferrin, suggesting that Rab14 and Rab4 regulate endosomal functions through cooperative interactions with their dual effector, RUFY1.

Research Products

• [Journal Article] Arfaptins are localized to the trans-Golgi by interaction with Arl1, but not Arfs. (2010)
  • Author(s): Man, Z., Kondo, Y., Koga, H., Umino, H., Nakayama, K., Shin, H.-W.
  • Journal Title: J.Biol.Chem. (In press.)
  • Peer Reviewed
• [Journal Article] Functional cross-talk between Rab14 and Rab4 through a dual effector, RUFY1/Rabip4. (2010)
  • Author(s): Yamamoto, H., Koga, H., Katoh, Y., Takahashi, S., Nakayama, K., Shin, H.-W.
  • Journal Title: Mol.Biol.Cell 21 Pages: 2746-2755
  • Peer Reviewed
• [Journal Article] Three homologous ArfGAPs participate in COPI-mediated transport. (2009)
  • Author(s): Saitoh, A., Shin, H.-W., Yamada, A., Waguri, S., Nakayama, K.
  • Journal Title: J.Biol.Chem. 284 Pages: 13948-13957
  • Peer Reviewed
• [Journal Article] Differential effects of depletion of ARL1 and ARFRP1 on membrane trafficking between the trans-Golgi network and endosomes. (2009)
  • Author(s): Nishimoto-Morita, K., Shin, H.-W., Mitsuhashi, H., Kitamura, M., Zhang, Q, Johannes, L., Nakayama, K.
  • Journal Title: J.Biol.Chem. 284 Pages: 10583-10592
  • Peer Reviewed
• [Journal Article] Retroendocytosis pathway of ABCA1/apoA-I contributes to HDL formation. (2009)
  • Author(s): Azuma, Y., Takada , M., Shin, H.-W., Kioka, N., Nakayama, K., Ueda, K.
  • Journal Title: Genes Cells 14 Pages: 191-204
  • Peer Reviewed
• [Presentation] Functional crosstalk between Rab14 and Rab4 through a dual effector, RUFY1/Rabip4. (2010)
  • Author(s): Hye-Won Shin
  • Organizer: 50^<th> Annual meeting of American Society for Molecular Cell Biology
  • Place of Presentation: アメリカ合衆国、フィラデルフィア
  • Year and Date: 2010-12-14
• [Presentation] RUFY1/Rabip4を介したRab14とRab4のクロストーク (2010)
  • Author(s): Hye-Won Shin
  • Organizer: BMB2010(第33回日本分子生物学会、第83回日本生化学会合同大会)
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Roles of Small GTPase ARF1 and ARF3 in recycling endosomes. (2010)
  • Author(s): Hye-Won Shin,
  • Organizer: FASEB meeting 'Arf small GTPases'
  • Place of Presentation: アメリカ合衆国、アリゾナ、Carefree
  • Year and Date: 2010-08-18
• [Presentation] RUFY1 (Rabip4)によるRab14とRab4のクロストーク (2009)
  • Author(s): Hye-Won Shin
  • Organizer: 第1回細胞内ロジスティクス全体班会議、ANAインターコンチネンタル万座ビーチリゾート
  • Place of Presentation: 沖縄
  • Year and Date: 2009-11-10
• [Presentation] Small GTPase ARF3 is involved in lysosomal degradation pathway. (2009)
  • Author(s): Hye-Won Shin
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2009-06-02
• [Remarks] ホームページ等
  • URL: http://www.cp.kyoto-u.ac.jp/HShin/ShinIndex.html