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Novel regulatory mechanism of semaphorin in endosomal trafficking

Research Project

Project/Area Number 23390069
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionOsaka University

Principal Investigator

TOYOFUKU Toshihiko  大阪大学, 免疫学フロンティア研究センター, 准教授 (60322179)

Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywordsセマフォリン / 網膜色素変性症 / 網膜色素上皮 / 色素上皮細胞 / 視細胞 / semaphorin 4A / 網膜色素上皮細胞 / Sema4A / 細胞内膜輸送制御
Research Abstract

Sema4A was identified in a family suffering from retinitis pigmentosa (RP). We generated the Sema4A-deficient mice and found the degeneration of photoreceptors. This result supported the hypothesis that Sema4A is the one of the causative genes for the human retinitis pigmentosa. Retinal pigment epithelial cells (RPE), where Sema4A is expressed, prevent photoreceptors from light-induced apoptosis and support the retinoid recycling which regenerates the photo-converted retinoid to normal one. Sema4A was found to activate these processes through regulating the endosomal trafficking. We further generated the mice carrying the mutated Sema4A, which were identified in human RP and found that these mutations in Sema4A are responsible for the RP. The injection of retrovirus carrying wild-type Sema4A successfully rescued the defects in photoreceptors in mutated mice. This result provided the possibility that the RP can be improved by the gene-transfer of Sema4A into RPE.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (11 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results) Presentation (4 results) Book (3 results)

  • [Journal Article] A point mutation in Semaphorin 4A associates with defective Endosomal sorting and causes retinal degenerative diseases2013

    • Author(s)
      Nojima S, Toyofuku T, Kamao H, Ishigami C, Kaneko J, Okuno T, Takamatsu H, Ito D, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Ogata A, Ikawa M, Morii E, Aozasa K, Takagi J, Takahashi M, Kumanogoh A
    • Journal Title

      Nat Commun

      Volume: 4 Pages: 1406-1406

    • Related Report
      2013 Final Research Report
  • [Journal Article] A point mutation in Semaphorin 4A associates with defective endosomal sorting and causes retinal degeneration2013

    • Author(s)
      Nojima S, et al.
    • Journal Title

      Nat Commun

      Volume: 4 Issue: 1 Pages: 1406-1406

    • DOI

      10.1038/ncomms2420

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endosomal sorting by Semaphorin 4A in retinal pigment epithelium supports photoreceptor survival2012

    • Author(s)
      Toyofuku T, Nojima S, Ishikawa T, Takamatsu H, Tsujimura T, Uemura A, Matsuda J, Seki T, Kumanogoh A
    • Journal Title

      Genes Dev

      Volume: 26(8) Pages: 816-29

    • Related Report
      2013 Final Research Report
  • [Journal Article] Endosomal sorting by Semaphorin 4A in retinal pigment epithelium supports photoreceptor survival.2012

    • Author(s)
      Toyofuku T, Nojima S, Ishikawa T, Takamatsu H, Tsujimura T, Uemura A, Matsuda J, Seki T, Kumanogoh A
    • Journal Title

      Genes Dev

      Volume: 26 Issue: 8 Pages: 816-829

    • DOI

      10.1101/gad.184481.111

    • Related Report
      2012 Annual Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Presentation] Endosormal sorting by Semaphorin 4A in retinal pigment epithelium supprts photoreceptor survival2011

    • Author(s)
      Toshihiko Toyofuku
    • Organizer
      34日本分子生物学会
    • Place of Presentation
      パシフィコ横浜{神奈川県}(ワークショップ)
    • Year and Date
      2011-12-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Semaphorin 4Aによる網膜色素上皮細胞内の膜輸送制御は光受容体維持に重要である2011

    • Author(s)
      豊福利彦
    • Organizer
      84回日本生化学会大会
    • Place of Presentation
      国立京都国際会館{京都府}(シンポジウム)
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] Semaphorin 4A による網膜色素上皮細胞内の膜輸送制御は光受容体維持に重要である

    • Author(s)
      豊福利彦
    • Organizer
      84回日本生化学会大会
    • Place of Presentation
      シンポジウム
    • Related Report
      2013 Final Research Report
  • [Presentation] Endosormal sorting by Semaphorin 4A in retinal pigment epithelium supprts photoreceptor survival

    • Author(s)
      Toshihiko Toyofuku
    • Organizer
      34日本分子生物学会
    • Place of Presentation
      ワークショップ
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学2013

    • Author(s)
      豊福利彦
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
  • [Book] 遺伝子医学MOOK別冊2013

    • Author(s)
      豊福利彦、熊ノ郷淳
    • Total Pages
      7
    • Publisher
      メディカルデュ
    • Related Report
      2013 Annual Research Report
  • [Book] 医学のあゆみ2013

    • Author(s)
      森本桂子、豊福利彦
    • Total Pages
      6
    • Publisher
      医歯薬出版
    • Related Report
      2013 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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