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Analysis of the Sterol Sensing Domain Containing proteins during development

Research Project

Project/Area Number 17570182
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionHyogo College of Medicine

Principal Investigator

NAKANO Yoshiro  Hyogo College of Medicine, Faculty of Medicine, Assistant Professor (30360267)

Co-Investigator(Kenkyū-buntansha) YAMAMOTO Daisuke  Tohoku University, Graduate School of Life Science, Professor (50318812)
UMEDA Masato  Kyoto University, Institute for Chemical Research, Professor (10185069)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordssterol-sensing / patched / hedgehog / patched-related / ステロールセンシングドメイン / ptr / ヘッジホッグ
Research Abstract

Transmembrane protein Patched (Ptc) binds to Hedgehog (Hh) proteins and regulates the activity of Smoothened (Smo). Ptc contains a sterol-sensing domain (SSD) found in proteins involved in cholesterol homeostasis or trafficking. We earlier reported finding that two missense mutations in the SSD of Drosophila patched exhibit a clear dominant negative effect. Here we tested and analyzed in vivo the function of Basal Cell Nevus Syndrome missense mutations of human PTCH1 gene generating transgenic flies carrying corresponding Drosophila patched mutations. When we missexpressed all three mutations, G500V D504Y G500R, they behaved similar to wild-type patched. However none of them could rescue ptc mutant embryos. This finding suggested that not all SSD mutations act with a dominant negative and that the GxxxD motif in PTCH1 is essential for the protein function.
To further elucidate SSD functions, we searched Drosophila and mouse genomes and identified a new SSD containing a gene in Drosophila (Ptr: CG11212) and four new SSD containing genes in mouse (Ptchd1 Ptchd2 Ptchd3 Ptchd4). All genes were cloned and sequenced. Their expressions were then analyzed by RT-PCR and in situ hybridization. Ptchd1 expression was observed in cerebellar primordium at E13 embryos, Ptchd2 expression in myelencephalon and spinal cord after E11, while Ptchd3 expression was restricted in spermatocyte of adult testis.
Drosophila Ptr expression is very dynamic. Transcripts are detected at the germ layers except in the future mesoderm region at blastoderm stage. Later the expression becomes segmental. Anti-Ptr antibody analyses showed that Ptr protein was localized in cystoblasts and oocytes in ovary, while Ptr is detected later in centrosomes at stage 5 embryos. These expression patterns predict that one of the functions of Ptr family genes is involved in germ cell formation.

Report

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

    (7 results)

All 2006 2005

All Journal Article (7 results)

  • [Journal Article] The ratio of phosphatidylcholine to phosphatidylethanolamine influences membrane integrity and steatohepatitis.2006

    • Author(s)
      Li Z
    • Journal Title

      Cell Metabolism 3・5

      Pages: 321-331

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.2006

    • Author(s)
      Yoshikawa R
    • Journal Title

      World J.Gastroenterology 12・36

      Pages: 5884-5889

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Targeted expression of ip(3) sponge and ip(3)dsrna impaires sugar taste sensation in Drosophila2005

    • Author(s)
      Usui-Aoki K
    • Journal Title

      J Neurogenet 19(3)

      Pages: 123-141

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fruitless specifies sexually dimorphic neural circuitry in the Drosophila brain.2005

    • Author(s)
      Kimura K
    • Journal Title

      Nature 438(7065)

      Pages: 229-233

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Species-specific patterns of sexual dimorphism in the expression of fruitless protein, a neural musculinizing factor in Drosophila2005

    • Author(s)
      Usui-Aoki K
    • Journal Title

      J Neurogenet. 19(2)

      Pages: 109-121

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Functional replacement of Drosophila Btk29A with human Btk in male genital development and survival.2005

    • Author(s)
      Hamada N
    • Journal Title

      FEBS Lett. 579(19)

      Pages: 4131-4137

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Local change in phospholipid composition at the cleavage furrow is essential for completion of cytokinesis.2005

    • Author(s)
      Emoto K
    • Journal Title

      J Biol Chem 280(45)

      Pages: 37901-37907

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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