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2003 Fiscal Year Final Research Report Summary

Molecular Mechanisms of L1-dependnet axon growth (intracellular L2-trafficking and signaling pathways)

Research Project

Project/Area Number 13680857
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

KAMIGUCHI Hiroyuki  RIKEN, Neuronal Growth Mechanisms, Lab.Head, 神経成長機構研究チーム, チームリーダー (10233933)

Project Period (FY) 2001 – 2003
Keywordsaxon / growth cone / cell adhesion molecule / L1 / endocytosis / ankyrin / molecular clutch / lipid raft
Research Abstract

In the developing nervous system, central and peripheral axon tracts are formed by axons that have elongated from the neuronal soma and reached their appropriate targets. Various cell adhesion molecules (CAMs) expressed on the growing axon and its tip (the growth Cone) interact with environmental cues, regulate growth cone motility, and navigate the axon along the correct path. In this research project, we have analyzed the functions of the immunoglobulin superfamily CAM Li and its interacting protein, ankyrin_B, and obtained the following results : 1.Ankyrin_B functions as a molecular clutch that connects retrograde F-actin flow with the L1 cytoplasmic domain (L1CD), thereby transmitting traction force that drives neurite initiation. 2.After moving into the central domain of growth cones by coupling with retrograde F-actin flow, L1 is endocytosed via the AP-2 and clathrin-mediated pathway followed by recycling to the plasma membrane of the growth cone leading edge. This type of intracellular L1 trafficking is required to create and maintain a gradient of L1-mediated adhesion (strong adhesion at the front and weak adhesion at the rear) in growth cones. It is also required for anterograde migration of the growth cones. 3.L1 interaction with AP-2 is regulated by phosphorylation/dephosphorylation of Tyr^<1176> in the L1CD. Clathrin-mediated endocytosis of L1 is triggered by the tyrosine dephosphorylation. 4.This tyrosine can be phosphorylated by the non-receptor tyrosine kinase Src that is localized to lipid rafts, specialized membrane microdomains enriched in cholesterol and sphingolipids. 5.Lipid rafts in the growth cone peripheral domain are critical for L1-based axon growth. These results help to understand the molecular mechanisms of axon growth.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Hiroyuki Kamiguchi: "The Role of Endocytic L1 Trafficking in Polarized Adhesion and Migration of Nerve Growth Cones"The Journal of Neuroscience. 21・23. 9194-9203 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Andrew W.Schaefer: "L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1"The Journal of Cell Biology. 157・7. 1223-1232 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yoko Nakai: "Migration of nerve growth cones requires detergent-resistant membranes in a spatially-defined and substrate-dependent manner"The Journal of Cell Biology. 159・6. 1097-1108 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kazunari Nishimura: "L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow"The Journal of Cell Biology. 163・5. 1077-1088 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Kamiguchi: "The mechanism of Axon Growth"Molecular Neurobiology. 28・3. 219-227 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 上口裕之: "神経成長円錐の移動メカニズム"生体の科学. 55・1. 14-19 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 塩坂貞夫: "動くシナプスと神経ネットワーク"金芳堂. 181 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiroyuki Kamiguchi: "The Role of Endocytic L1 Trafficking in Polarized Adhesion and Migration of Nerve Growth Cones"The Journal of Neuroscience. 21・23. 9194-9203 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Andrew W.Schaefer: "L1 endocytosis is controlled by a phosphorylation-dephosphorylation cycle stimulated by outside-in signaling by L1"The Journal of Cell Biology. 157・7. 1223-1232 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoko Nakai: "Migration of nerve growth cones requires detergent-resistant membranes in a spatially-defined and substrate-dependent manner"The Journal of Cell Biology. 159・6. 1097-1108 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kazunari Nishimura: "L1-dependent neuritogenesis involves ankyrinB that mediates L1-CAM coupling with retrograde actin flow"The Journal of Cell Biology. 163・5. 1077-1088 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyuki Kamiguchi: "The mechanism of Axon Growth"Molecular Neurobiology. 28・3. 219-227 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiroyuki Kamiguchi: "The mechanisms of neuronal growth cone motility"Seitai No Kagaku. 55・1. 14-19 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sadao Shiosaka: "Synaptic dynamics and neuronal network"Kinppo Do. 181 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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