Isolation and characterization of protrudin, a master regulator of neurite formation

2009 Fiscal Year Final Research Report

• Project/Area Number: 17107004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Cell biology
• Research Institution: Kyushu University
• Principal Investigator: NAKAYAMA Keiichi Kyushu University, 生体防御医学研究所, 主幹教授 (80291508)
• Co-Investigator(Kenkyū-buntansha): SHIRANE Michiko 九州大学, 生体防御医学研究所, 准教授 (90398082)
• Project Period (FY): 2005 – 2009
• Keywords: 神経細胞 / 神経突起 / 膜輸送 / Gタンパク質 / リン酸化 / 神経成長因子

Research Abstract

Guanosine triphosphatases (GTPases) of the Rab family are key regulators of membrane trafficking, with Rab11 playing a specific role in membrane recycling. We identified a protein, protrudin, that promoted neurite formation through interaction with the guanosine diphosphate (GDP)-bound form of Rab11. Phosphorylation of protrudin by extracellular signal-regulated kinase (ERK) in response to nerve growth factor promoted its association with Rab11-GDP. Down-regulation of protrudin by RNA interference induced membrane extension in all directions and inhibited neurite formation. Thus protrudin regulates Rab11-dependent membrane recycling to promote the directional membrane trafficking required for neurite formation.

Research Products

• [Journal Article] KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development. (2010)
  • Author(s): Tsukada, Y., Ishitani, T., Nakayama, K.I.
  • Journal Title: Genes Dev 24 Pages: 432-437
• [Journal Article] Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. (2010)
  • Author(s): Lin, H.K., Chen, Z., Wang, G., Nardella, C., Lee, S.W., Chan, C.H., Yang, W.L., Wang, J., Egia, A., Nakayama, K.I., Cordon-Cardo, C., Teruya-Feldstein, J., Pandolfi, P.P.
  • Journal Title: Nature 464 Pages: 374-379
• [Journal Article] Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis. (2010)
  • Author(s): Chan, C.H., Lee, S.W., Li, C.F., Wang, J., Yang, W.L., Wu, C.Y., Wu, J., Nakayama, K.I., Kang, H.Y., Huang, H.Y., Hung, M.C., Pandolfi, P.P., Lin, H.K.
  • Journal Title: Nature Cell Biol.
• [Journal Article] Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/-mice. (2010)
  • Author(s): Wang, H., Bauzon, F., Ji, P., Xu, X., Sun, D., Locker, J., Sellers, R.S., Nakayama, K., Nakayama, K.I., Cobrinik, D., Zhu, L.
  • Journal Title: Nature Genet. 42 Pages: 83-88
• [Journal Article] CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment during early embryogenesis. (2009)
  • Author(s): Nishiyama, M., Oshikawa, K., Tsukada, Y., Nakagawa, T., Iemura, S., Natsume, T., Fan, Y., Kikuchi, A., Skoultchi, A.I., Nakayama, K.I.
  • Journal Title: Nature Cell Biol. 11 Pages: 172-182
• [Journal Article] Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. (2009)
  • Author(s): Lin, H.K., Wang, G., Chen, Z., Teruya-Feldstein, J., Liu, Y., Chan, C.H., Yang, W.L., Erdjument-Bromage, H., Nakayama, K.I., Nimer, S., Tempst, P., Pandolfi, P.P.
  • Journal Title: Nature Cell Biol. 11 Pages: 420-432
• [Journal Article] Common and specific roles of the related CDK inhibitors p27 and p57 revealed by a knock-in mouse model. (2009)
  • Author(s): Susaki, E., Nakayama, K., Yamasaki, L., Nakayama, K.I.
  • Journal Title: Proc. Natl. Acad. Sci. U.S.A. 106 Pages: 5192-5197
• [Journal Article] Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. (2007)
  • Author(s): Onoyama, I., Tsunematsu, R., Matsumoto, A., Kimura, T., de Alboran, I.M., Nakayama, K., Nakayama, K.I.
  • Journal Title: J. Exp. Med. 204 Pages: 2875-2888
• [Journal Article] Mitogenic signalling and the p16INK4a-Rb pathway cooperate to enforce irreversible cellular senescence. (2006)
  • Author(s): Takahashi, A., Ohtani, N., Yamakoshi, K., Iida, S., Tahara, H., Nakayama, K., Nakayama, K.I., Ide, T., Saya, H., Hara, E.
  • Journal Title: Nature Cell Biol. 8 Pages: 1291-1297
• [Journal Article] Protrudin induces neurite formation by directional membrane trafficking. (2006)
  • Author(s): Shirane, M., Nakayama, K.I.
  • Journal Title: Science 314 Pages: 818-821
• [Presentation] Comprehensive elucidation of enzyme-substrate relationship in ubiquitylation by differential proteomics: Say good-bye to western blotting. (2010)
  • Author(s): Nakayama, K.I.
  • Organizer: Biology of the ubiquitin and the ubiquitin-like systems.
  • Place of Presentation: Jerusalem
  • Year and Date: 2010-03-14
• [Presentation] Comprehensive elucidation of enzyme-substrate relationship by differential proteomics. (2009)
  • Author(s): Nakayama, K.I., Yumimoto, K., Matsumoto, M.
  • Organizer: The 4th International Workshop on Cell Regulations in Division and Arrest.
  • Place of Presentation: Onna, Okinawa, Japan
  • Year and Date: 2009-12-02
• [Presentation] Two F-box prtoteins Skp2 and Fbw7 control cell cycle exit and re-entry. (2008)
  • Author(s): Nakayama, K. I
  • Organizer: ZOMES V: The Fifth International Symposium on the COP9 signalosome, Proteasome, and eIF3: At the interface between signaling & proteolysis.
  • Place of Presentation: Yokohama
  • Year and Date: 2008-11-12
• [Presentation] Cell cycle control during T-cell development. (2008)
  • Author(s): Nakayama, K.I.
  • Organizer: Japan-German Immunology Seminar "International Conference on Immune Regulation in Health and Disease"
  • Place of Presentation: Fukuoka
  • Year and Date: 2008-11-05
• [Presentation] プロトルーディンはRab11-GDPに結合し、特定の方向へ向かう膜輸送により神経突起形成を起こす. (2008)
  • Author(s): 中山敬一, 白根道子
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-30
• [Presentation] Conditional inactivation of Fbxw7 results in a defect in cell cycle exit and tumorigenesis. (2008)
  • Author(s): Nakayama, K.I., Onoyama, I., Tsunematsu, R., Matsumoto, A., Nakayama, K.
  • Organizer: Cold Spring Harbor Symposium "The Cell Cycle"
  • Place of Presentation: Cold Spring Harbor, NY
  • Year and Date: 2008-05-18
• [Presentation] Fbw7 is required for G0 maintenance and tumor suppression: Lessons from a series of conditional knockout mice. (2007)
  • Author(s): Nakayama, K.I.
  • Organizer: The Second International Workshop on Cell Regulations in Division and Arrest
  • Place of Presentation: Onna, Okinawa, Japan
  • Year and Date: 2007-03-26
• [Presentation] Fbw7 is a key regulator of cell cycle exit during development. (2006)
  • Author(s): Nakayama, K.I.
  • Organizer: US-Japan Cooperative Research Workshop on Mouse Models for Cell Cycle and Ubiquitin-mediated Degradation
  • Place of Presentation: Frederick, MD, USA
  • Year and Date: 2006-09-07
• [Presentation] Fbw7 is a key regulator of cell-cycle arrest and tumorigenesis during development. (2006)
  • Author(s): Nakayama, K.I., Onoyama, I.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2006-06-23
• [Presentation] Protrudin-Rab11 system regulates directional membrane traffic to induce neurite formation. (2005)
  • Author(s): Nakayama, K.I., Shirane, M.
  • Organizer: International Symposium on "Membrane Dynamics and Cell Regulation"
  • Place of Presentation: Fukuoka
  • Year and Date: 2005-06-29
• [Book] 細胞周期:細胞増殖の制御メカニズム. 細胞周期:細胞増殖の制御メカニズム(中山敬一, 中山啓子編) (2008)
  • Author(s): 中山敬一, 中山啓子
  • Total Pages: メディカル・サイエンス・インターナショナル
  • Publisher: 東京
• [Book] 細胞周期ブレーキp27の分解と発がん. 発がんの分子機構と防御(笹月健彦, 野田哲生編)
  • Author(s): 中山敬一
  • Publisher: 東京大学出版会(東京)
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/saibou/index.html
• [Patent(Industrial Property Rights)] タンパク質の定量方法 (2006)
  • Inventor(s): 中山敬一、松本雅記
  • Industrial Property Rights Holder: 国立大学法人九州大学
  • Industrial Property Number: 特許・特願2009-169045
  • Filing Date: 2006-06-09