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Regulation of axon growth and guidance by lipid rafts

Research Project

Project/Area Number 16500210
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neuroscience in general
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) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsaxon / growth cone / lipid raft / L1 / adhesion molecule / exocytosis / 神経 / 膜小胞 / VAMP2 / 小脳 / プロテオミクス
Research Abstract

During development, the tip of axons, called the growth cone, expresses various functional molecules that regulate axon elongation and guidance. In cell membranes, proteins and lipids are not uniformly distributed but form spatially differentiated microdomains, such as lipid rafts composed predominantly of cholesterol and sphingolipids. It has been reported that the cell adhesion molecule L1, a transmembrane protein involved in axon elongation, is localized to lipid rafts and that rafts in the growth cone periphery is critical for axon elongation (J Cell Biol 159 : 1097-1108, 2002). In this project, we have conducted differential proteomic studies to search for proteins that translocate into or out of lipid rafts in response to ligand binding to L1 expressed on neurons in culture. These studies identified two proteins, munc-18 and synaptophysin, both of which are implicated in the regulation of membrane exocytosis. Therefore, we next investigated the role of membrane exocytosis in axon growth and guidance. Endocytic vesicles in growth cones were labeled with FM1-43 and their movement was monitored. We found that the growth cone turning is accompanied by selective transport of endocytic vesicles to the side facing the new direction. VAMP2-positive exocytosis-competent vesicles showed the similar pattern of movement. We also found that the transported vesicles are exocytosed at the growth cone periphery. This work has demonstrated that the growth cone turns by preferentially supplying membrane components to the side facing the new direction and suggested that lipid rafts could be involved in the regulation of membrane exocytosis.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 2005 2004 Other

All Journal Article (21 results) Book (2 results)

  • [Journal Article] Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone.2007

    • Author(s)
      Takuro Tojima
    • Journal Title

      Nat Neurosci 10・1

      Pages: 58-66

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Serine phosphorylation by casein kinase II controls endocytic L1 trafficking and axon growth.2007

    • Author(s)
      Asuka Nakata
    • Journal Title

      J Neurosci Res 85・4

      Pages: 723-734

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Serine phosphorylation by casei kinase II controls endocytic LI trafficking and axon growth.2007

    • Author(s)
      Asuka Nakata
    • Journal Title

      Neurosci Res 85・4

      Pages: 723-734

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Attractive axon guidance involves asymmetric membrane transport and exocytosis in the growth cone.2007

    • Author(s)
      Tojima T
    • Journal Title

      Nature Neurosci 10・1

      Pages: 58-66

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The region-specific activities of lipid rafts during axon growth and guidance.2006

    • Author(s)
      Hiroyuki Kamiguchi
    • Journal Title

      J Neurochem 98・2

      Pages: 330-335

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Sphingolipid Biology.2006

    • Author(s)
      Hiroyuki Kamiguchi
    • Journal Title

      Springer-Verlag 531

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular mechanisms and neuroradiological criteria for the X-linked hydrocephalus type of severe L1 syndrome.2006

    • Author(s)
      Kanemura Y
    • Journal Title

      J Neurosurg 105・5

      Pages: 403-412

    • Related Report
      2006 Annual Research Report
  • [Journal Article] The region-specific activities of lipid rafts during axon growth and guidance.2006

    • Author(s)
      Kamiguchi H
    • Journal Title

      J Neurochem 98・2

      Pages: 330-335

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 神経接着分子L1による神経突起成長の力学的メカニズム.2006

    • Author(s)
      上口裕之
    • Journal Title

      蛋白質 核酸 酵素 51・6

      Pages: 623-628

    • Related Report
      2006 Annual Research Report
  • [Journal Article] First case of L1CAM gene mutation identified in MASA syndrome in Asia.2005

    • Author(s)
      Kanemura Y
    • Journal Title

      Congenit Anom 45・2

      Pages: 67-69

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Disrupted Schwann cell-axon interactions in peripheral nerves of mice with altered L1-integrin interactions.2005

    • Author(s)
      Itoh K
    • Journal Title

      Mol Cell Neurosci 30・1

      Pages: 131-136

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cell adhesion molecules regulate Ca^<2+>-mediated steering of growth cones via cyclic AMP and ryanodine receptor type 3.2005

    • Author(s)
      Ooashi N
    • Journal Title

      J Cell Biol 170・7

      Pages: 1159-1167

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 先天性水頭症の分子生物学(2)神経接着分子2005

    • Author(s)
      上口裕之
    • Journal Title

      脳21 8・2

      Pages: 123-128

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 成長円錐脂質ラフトによる神経軸索身長制御2004

    • Author(s)
      上口裕之
    • Journal Title

      細胞工学 23・9

      Pages: 1044-1046

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The regulation of axon elongation by lipid rafts in the growth cone.2004

    • Author(s)
      Hiroyuki Kamiguchi
    • Journal Title

      Cell Technology 23・9

      Pages: 1044-1046

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 神経成長円錐の移動メカニズム2004

    • Author(s)
      上口裕之
    • Journal Title

      生体の化学 55・1

      Pages: 14-19

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 成長円錐脂質ラフトによる神経軸索伸長制御2004

    • Author(s)
      上口裕之
    • Journal Title

      細胞工学 23・9

      Pages: 1044-1046

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 神経軸索ガイダンスを制御する細胞内シグナル伝達のダイナミクス2004

    • Author(s)
      戸島拓郎
    • Journal Title

      実験医学 22・15

      Pages: 2130-2135

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 神経軸索成長を制御する分子クラッチ機構2004

    • Author(s)
      西村一成
    • Journal Title

      蛋白質 核酸 酵素 49・14

      Pages: 2206-2214

    • Related Report
      2004 Annual Research Report
  • [Journal Article] βIV-spectrin forms a diffusion barrier against L1CAM at the axon initial segment.

    • Author(s)
      Nishimura K
    • Journal Title

      Mol Cell Neurosci (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serine phosphorylation by casein kinase II controls endocytic L1 trafficking and axon growth.

    • Author(s)
      Nakata A
    • Journal Title

      J Neurosci Res (in press)

    • Related Report
      2006 Annual Research Report
  • [Book] Sphingolipid Biology.2006

    • Author(s)
      Hiroyuki Kamiguchi
    • Total Pages
      531
    • Publisher
      Springer-Verlag
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] Sphingolipid Biology.2006

    • Author(s)
      Kamiguchi H
    • Total Pages
      531
    • Publisher
      The role of lipid rafts in axon growth and guidance.
    • Related Report
      2006 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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