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2007 Fiscal Year Final Research Report Summary

Molecular mechanism underlying cell polarity and cell migration

Research Project

Project/Area Number 15GS0319
Research Category

Grant-in-Aid for Creative Scientific Research

Allocation TypeSingle-year Grants
Research InstitutionNagoya University

Principal Investigator

KAIBUCHI Kozo  Nagoya University, Graduate School of Medicine, Professor (00169377)

Co-Investigator(Kenkyū-buntansha) USUKURA Jiro  Nagoya University, Center for Cooperative Research in Advanced Science&Technology, Professor (30143415)
KURODA Shinya  University of Tokyo, Graduate School of Science, Professor (50273850)
AMANO Mutsuki  Nagoya University, Graduate School of Medicine, Associate Professor (90304170)
TAYA Shinichiro  Nagoya University, Graduate School of Medicine, Associate Professor (60362232)
ARIMURA Nariko  Tamagawa University, Brain Science Institute, COE Associate Professor (20420375)
Project Period (FY) 2003 – 2007
Keywordspolarily / axon / migration / CRMP-2 / Rho family / signal transduction / simulation / contraction
Research Abstract

Cell polarization is an essential step for cellular functions, but the underlying mechanisms to establish and maintain cell polarity are not fully understood. We tried to clarify the signal transduction mechanisms controlling cell polarization by the use of cell migration and neuronal axon/dendrite determination as model systems.
1. Identification of extracellular signals modulating neuronal polarity and following signaling pathways.
Extracellular signals such as laminin induced the production of PIP3, inactivation of GSK-3β, and resultant activation of CRMP-2. Active CRMP-2 bound to tubulin, Sra-1, and Numb, and regulated tubulin polymerization, actin remodeling, and L1 endocytosis at growth cone, which contributed to the axon elongation and neuronal axon/dendrite determination. In addition, Par complex composed of Par-3, Pare and aPKC modulated the Rac activity through Rac GEF (Tiam1/Tiam2) to establish neuronal polarity and front-rear polarity of migrating cells.
2. Analysis of signali … More ng pathways underlying cell migration
During establishment and maintenance of front-rear polarity in cell migration, Rac/IAGAP1 regulated dynamics of both actin and microtubules through APC/CLIP-170. Rho/Rho-kinase inhibited Par complex formation and adjusted the Rac activity properly both at the front and rear.
3. Role of molecular and vesicular traffic in cell polarization and migration
CRMP-2 interacted with tubulin, Sra-1 and Slp1/TrkB, and transported them to the tip of axon as a “cargo receptor". Numb regulated integrin endocytosis at the front of migrating cell, which is supposed to be necessary for directional migration.
4. Analysis of signal networks by computer simulation
The computational model for endothelial cell contraction (activation of myosin) suggested the existence of unidentified pathway for sustained cell contraction in silico, and the novel pathway mediated by iPLA2 was identified in vivo. The computational model for establishment of front-rear polarity of migrating cells by Rho family GTPases was developed. Less

  • Research Products

    (39 results)

All 2009 2008 2007 2006 2005 2004 2003 Other

All Journal Article (22 results) (of which Peer Reviewed: 11 results) Presentation (14 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Anterograde transport of TrkB in axons is mediated by direct interaction with Slpl and Rab27.2009

    • Author(s)
      Arimura, N., et al.
    • Journal Title

      Dev Cell (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Anterograde Transport of TrkB in Axons is Mediated by Direct Interaction with Slp1 and Rab27.2009

    • Author(s)
      Arimura N., et al
    • Journal Title

      Dev Cell (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Rho-kinase phosphorylates PAR-3 and disrupts PAR complex formation.2008

    • Author(s)
      Nakayama, M., et al.
    • Journal Title

      Dev Cell 14

      Pages: 205-215

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Rho-kinase phosphorylates PAR-3 and disrupts PAR complexformation.2008

    • Author(s)
      Nakayama M., et al
    • Journal Title

      Dev Cell 14

      Pages: 205-215

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A mass conserved reaction-diffusion system captures properties of cell polarity.2007

    • Author(s)
      Otsuji, M., et al.
    • Journal Title

      PLoS Comput Biol 3

      Pages: e108

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3.2007

    • Author(s)
      Nishimura, T., et al.
    • Journal Title

      Dev Cell 13

      Pages: 15-28

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Neuronal polarity : from extracellular signals to intracellular mechanisms.2007

    • Author(s)
      Arimura, N., et al.
    • Journal Title

      Nat Rev Neurosci 8

      Pages: 194-205

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] A mass conserved reaction-diffusion system captures properties of cell polarity.2007

    • Author(s)
      Otsuji M., et al
    • Journal Title

      PLosS Comput Biol 3

      Pages: e108

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3.2007

    • Author(s)
      Nishimura T., et al
    • Journal Title

      Dev Cell 13

      Pages: 15-28

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Neuronal polarity: from extracellular signals to intracellular mechanisms.2007

    • Author(s)
      Arimura N., et al
    • Journal Title

      Nat Cell Biol 8

      Pages: 194-205

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity.2005

    • Author(s)
      Yoshimura, T., et al.
    • Journal Title

      Cell 120

      Pages: 137-149

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiaml.2005

    • Author(s)
      Nishimura, T., et al.
    • Journal Title

      Nat Cell Biol 7

      Pages: 270-277

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Key regulators in neuronal polarity.2005

    • Author(s)
      Arimura, N., et al.
    • Journal Title

      Neuron 48

      Pages: 881-884

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] GSK-3beta regulates phosphorylation of CRMP-2 and neuronal polarity.2005

    • Author(s)
      Yoshimura T., et al
    • Journal Title

      Cell 120

      Pages: 137-149

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1.2005

    • Author(s)
      Nishimura T., et al
    • Journal Title

      Nat Cell Biol 7

      Pages: 270-277

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Key regulators in neuronal polarity.2005

    • Author(s)
      Arimura N., et al
    • Journal Title

      Neuron 48

      Pages: 270-277

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.2004

    • Author(s)
      Watanabe, T., et al.
    • Journal Title

      Dev Cell 7

      Pages: 871-883

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity.2004

    • Author(s)
      Nishimura, T., et al.
    • Journal Title

      Nat Cell Biol 6

      Pages: 328-334

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration.2004

    • Author(s)
      Watanabe T., et al
    • Journal Title

      Dev Cell 7

      Pages: 871-883

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Role of the PAR-3-KIF3 complex in the establishment of neuronal polarity.2004

    • Author(s)
      Nishimura T., et al
    • Journal Title

      Nat Cell Biol 6

      Pages: 328-334

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth.2003

    • Author(s)
      Nishimura, T., et al.
    • Journal Title

      Nat Cell Biol 5

      Pages: 819-826

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] CRMP-2 regulates polarized Numb-mediated endocytosis for axon growth.2003

    • Author(s)
      Nishimura T., et al
    • Journal Title

      Naat Cell Biol 5

      Pages: 819-826

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Neuronal polarity and small GTPases2008

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      FASEB summer research conference on small GTPases
    • Place of Presentation
      Vermont, USA
    • Year and Date
      20080713-20080718
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Neuronal polarity and small GTPases2008

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      FASEB summer research conference on small GTPases
    • Place of Presentation
      Vermont (USA)
    • Year and Date
      20080713-20080718
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Signaling networks in neuronal polarization2006

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Neuroscience 2006, symposium
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      20061014-20061018
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Signaling networks in neuronal polarization2006

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Neuroscience 2006, symposium
    • Place of Presentation
      Atlanta (USA)
    • Year and Date
      20061014-20061018
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Neuronal polarity and cytoskeleton2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      20th Biennial Meeting of International Society of Neurochemistry, symposium
    • Place of Presentation
      Innsbruck, Austria
    • Year and Date
      20050821-20050826
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Neuronal polarity and cytoskeleton2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      20th Biennial Meeting of International Society of Neurochemistry, symposium
    • Place of Presentation
      Innsbruck (Austria)
    • Year and Date
      20050821-20050826
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Signaling for Neuronal Polarity2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Keystone Symposia on cell migration and adhesion
    • Place of Presentation
      Utah, USA
    • Year and Date
      20050408-20050416
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Signaling for Neuronal Polarity2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Keystone Symposia on cell migration and adhesion
    • Place of Presentation
      Utah (USA)
    • Year and Date
      20050408-20050416
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Neuronal Polarity and Cytoskeleton2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Keystone Symposia on molecular and cellular biology
    • Place of Presentation
      Idaho, USA
    • Year and Date
      20050303-20050310
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Neuronal Polarity and Cytoskeleton2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Keystone Symposia on cell migration and adhesion
    • Place of Presentation
      Idaho (USA)
    • Year and Date
      20050303-20050310
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of Rho family in cell migration and polarity2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Nature Biotechnology Winter Symposium
    • Place of Presentation
      Miami, USA
    • Year and Date
      20050204-20050210
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Roles of Rho family in cell migration and polarity2005

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Nature Biotechnology Winter Symposium
    • Place of Presentation
      Miam (USA)
    • Year and Date
      20050204-20050210
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Roles of Rho family GTPases in cell polarization and directional migration2003

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      43^<th> Annual meeting of ASCB, symposium
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      20031211-20031216
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Roles of Rho family GTPases in cell polarization and directional migration2003

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      43^<th> Annual meeting of ASCB, symposium
    • Place of Presentation
      San Francisco (USA)
    • Year and Date
      20031211-20031216
    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 細胞骨格と接着2006

    • Author(s)
      貝淵弘三, 稲垣昌樹, 佐邊壽孝, 松崎文雄編
    • Total Pages
      323
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Cytoskeleton and Cell Adhesion2006

    • Author(s)
      Kaibuchi K., et al (ed)
    • Publisher
      Kyoritsu Shuppan Co., Ltd
    • Description
      「研究成果報告書概要(欧文)」より
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.med.nagoya-u.ac.jp/Yakuri/

URL: 

Published: 2010-06-09  

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