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Mechanisms of insect limb development

Research Project

Project/Area Number 15207018
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionRIKEN

Principal Investigator

HAYASHI Shigeo  RIKEN, Morphogenetic Signaling Group, Group Director, 生態形成シグナル研究グループ, グループディレクター (60183092)

Co-Investigator(Kenkyū-buntansha) TSUDA Leo  RIKEN, Morphogenetic Signaling Group, Researcher, 生態形成シグナル研究グループ, 研究員 (30333355)
INOUE Yoshiko  RIKEN, Morphogenetic Signaling Group, Researcher, 生態形成シグナル研究グループ, 研究員 (60217916)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2004: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Fiscal Year 2003: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
KeywordsSignaling / Drosophila / imaginal disc / Notch / Nedd4 / Deltex / endocytosis / ubiqitination / 付属肢 / エンドサイトーシス / ユビキチン / 成虫原基 / gfp / 気管 / 翅 / 細胞移動
Research Abstract

Ligand-induced proteolytic cleavage and internalization of the plasma membrane receptor Notch leads to its activation. Ligand-independent, steady state internalization of Notch, however, does not lead to activation. The mechanism by which downstream effectors discriminate these bipartite modes of Notch internalization is not understood. Nedd4 is a HECT domain-containing E3 ubiquitin ligase that targets transmembrane receptors containing the PPSY motif for endocytosis. Deltex is a positive regulator of Notch signaling and encodes a putative ubiquitin ligase of the ring finger type. We show that Notch is ubiquitinated, and destabilized by Nedd4 in a manner requiring the PPSY motif in the Notch intracellular domain. Loss of Nedd4 function dominantly suppresses the Notch and Deltex mutant phenotypes and its hyper activation attenuates Notch activity. In tissue culture cells, dominant-negative form of Nedd4 blocks steady-state Notch internalization and activates Notch signaling independently of ligand binding, and this effect was further potentiated by Deltex. Nedd4 destines Deltex to degradation in a Notch-dependent manner. Nedd4 antagonizes Notch signaling by promoting internalization of Notch and degradation of Notch and Deltex. Those functions of Nedd4 may be important for the protection of unstimulated cells from sporadic activation of Notch signaling.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2004 2003 Other

All Journal Article (13 results) Publications (3 results)

  • [Journal Article] Drosophila Nedd4 Regulates Endocytosis of Notch and Suppresses Its Ligand-Independent Activation2004

    • Author(s)
      Tadashi Sakata
    • Journal Title

      Current Biology 14

      Pages: 2228-2236

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the Drosophila trachea2004

    • Author(s)
      Kagayaki Kato
    • Journal Title

      Development 131

      Pages: 5253-5261

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Formin3 is required for assembly of the F-actin structure that mediates tracheal fuaion in Drosophila2004

    • Author(s)
      Hiromasa Tanaka
    • Journal Title

      Developmental Biology 274

      Pages: 413-425

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Drosophila Nedd4 regulates endocytosis of Notch and suppresses its ligand-independent activation.2004

    • Author(s)
      Sakata, Tadashi
    • Journal Title

      Current Biology 14

      Pages: 2228-2236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Hedgehog and Decapentaplegic instruct polarized growth of cell extensions in the Drosophila trachea.2004

    • Author(s)
      Kato, Kagayaki
    • Journal Title

      Development 131

      Pages: 5253-5261

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Formin3 is required for assembly of the F-actin structure that mediates tracheal fusion in Drosophila.2004

    • Author(s)
      Tanaka, Hiromasa
    • Journal Title

      Developmental Biology 274

      Pages: 413-425

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Formin3 is required for assembly of the F-actin structure that mediates tracheal fusion in Drosophila2004

    • Author(s)
      Hiromasa Tanaka
    • Journal Title

      Developmental Biology 274

      Pages: 413-425

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct Developmental modes and lesion-induced reactions of dentrites of two classes of Drosophila sensory neurons2003

    • Author(s)
      Sugimura Kaoru
    • Journal Title

      Journal of Neuroscience 23

      Pages: 3752-3760

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of Wg signaling in the patterning of embryonic leg primordium in Drosophila2003

    • Author(s)
      Kubota Kazumasa
    • Journal Title

      Developmental Biology 257

      Pages: 117-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila2003

    • Author(s)
      Chihara Takahiro
    • Journal Title

      Development 130

      Pages: 1419-1428

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Distinct developmental modes and lesion-induced reactions of dentrites of two classes of Drosophila sensory neurons2003

    • Author(s)
      Sugimura, Kaoru
    • Journal Title

      Journal of Neuroscience 23(9)

      Pages: 3752-3760

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The role of Wg signaling in the patterning of embryonic leg primordium in Drosophila.2003

    • Author(s)
      Kubota, Kazumasa
    • Journal Title

      Developmental Biology 257

      Pages: 117-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila.2003

    • Author(s)
      Chihara, Takahiro
    • Journal Title

      Development 130

      Pages: 1419-1428

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Sugimura, K: "Distinct developmental modes and lesion-induced reactions of dentrites of two classes of Drosophila sensory neurons"Journal of Neuroscience. 23. 3725-3760 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kubota, K: "The role of Wg signaling in the patterning of embiyonic leg primordium in Drosophila"Developmental Biology. 257. 117-126 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chihara, T: "Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila"Development. 130. 1419-1428 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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