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Selective activation of Wnt signaling pathway using with purified Wnt proteins

Research Project

Project/Area Number 23590333
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionOsaka University

Principal Investigator

YAMAMOTO Hideki  大阪大学, 医学(系)研究科(研究院), 准教授 (20372691)

Co-Investigator(Renkei-kenkyūsha) TAKAO Toshifumi  大阪大学, 蛋白質研究所, 教授 (10197048)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsWntシグナル経路 / Wnt / 受容体 / 翻訳後修飾 / 細胞内小胞輸送 / Wntシグナル / Wntless / 糖鎖修飾 / 極性分泌 / クラスリン / AP1 / AP2 / ガレクチン / Wnt11
Research Abstract

Wnts are glycan- and lipid-modified morphogens that are important for cellular responses, but how Wnt is secreted in polarized epithelial cells remains unclear. Here we show the apicobasal secretion of Wnts is regulated by different mechanisms. Wnt11 and Wnt3a were secreted apically and basolaterally, respectively, in polarized epithelial cells. Wntless was localized to the basolateral membrane. Mass-spectrometric analyses revealed that Wnt11 is modified with complex/hybrid-(Asn40), high-mannose-(Asn90), and high-mannose/hybrid-(Asn300) type glycans and that Wnt3a is modified with two high-mannose-type glycans (Asn87 and Asn298). Glycosylation processing at Asn40 and galectin-3 were required for the apical secretion of Wnt11, while clathrin and adaptor protein-1 were required for the basolateral secretion of Wnt3a. These results suggest that Wls has different roles on the polarized secretion of Wnt11 and Wnt3a and that glycosylation processing of Wnts decides their secretory routes

Report

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

    (22 results)

All 2013 2012 2011 Other

All Journal Article (10 results) (of which Peer Reviewed: 9 results) Presentation (6 results) Book (2 results) Remarks (4 results)

  • [Journal Article] The apical and basolateral secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by distinct mechanisms.2013

    • Author(s)
      Yamamoto, H., Awada, C., Hanaki, H., Sakane, H., Tsujimoto, I., Takahashi, Y., Takao, T., and Kikuchi, A.
    • Journal Title

      J. Cell Sci.

      Volume: 126 Pages: 2931-2943

    • DOI

      10.1242/jcs.126052

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 山本英樹, 菊池章2013

    • Journal Title

      極性化上皮細胞におけるWnt分泌制御細胞工学「Wnt協奏曲」

      Volume: 32巻4号 Pages: 388-395

    • Related Report
      2013 Final Research Report
  • [Journal Article] Apicobasal secretion of Wnt11 and Wnt3a in polarized epithelial cells is regulated by distinct mechanisms2013

    • Author(s)
      Yamamoto, H. et. al
    • Journal Title

      J. Cell Sci.

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Localization of glypican-4 in different membrane microdomains is involved in the regulation of Wnt signaling2012

    • Author(s)
      Sakane, H., et.al.
    • Journal Title

      J.Cell Sci.

      Volume: 125 Issue: 2 Pages: 449-460

    • DOI

      10.1242/jcs.091876

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] An Wnt5a-antibody suppresses metastasis of gastric cancer cells in vivo by inhibiting receptor-mediated endocytosis2012

    • Author(s)
      Hanaki, H., et.al.
    • Journal Title

      Mol.Cancer Ther.

      Volume: 11 Issue: 2 Pages: 298-307

    • DOI

      10.1158/1535-7163.mct-11-0682

    • Related Report
      2013 Final Research Report 2012 Research-status Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Wnt5a : its signaling, functions, and implication in diseases2012

    • Author(s)
      Kikuchi, A., et.al.
    • Journal Title

      Acta Physiol.

      Volume: 204 Issue: 1 Pages: 17-33

    • DOI

      10.1111/j.1748-1716.2011.02294.x

    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Wnt5a: its signaling, functions, and implication in diseases2012

    • Author(s)
      Kikuchi, A. et. al
    • Journal Title

      Acta physiol.

      Volume: 204 Pages: 17-33

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The transmembrane protein Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization2011

    • Author(s)
      Kagermeier-Schenk, B., Wehner, D., Ö z h a n -Kizil, G. Yamamoto, H., Li, J., Kirchner, K., Hoffmann, C., Stern, P., Kikuchi, A., Schambony, A., Weidinger, G.
    • Journal Title

      Dev. Cell

      Volume: 21 Issue: 4 Pages: 1129-1143

    • DOI

      10.1016/j.devcel.2013.07.020

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] New insights into the mechanism of Wnt signaling pathway activation2011

    • Author(s)
      Kikuchi, A
    • Journal Title

      Int Rev Cell Mol Biol.

      Volume: 291 Pages: 21-71

    • DOI

      10.1016/b978-0-12-386035-4.00002-1

    • ISBN
      9780123860354
    • Related Report
      2013 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization2011

    • Author(s)
      Kagermeier-Schenk, B., et.al.
    • Journal Title

      Dev.Cell.

      Volume: 21 Issue: 6 Pages: 1129-1143

    • DOI

      10.1016/j.devcel.2011.10.015

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 極性化された上皮細胞におけるWntの分泌制御機構2013

    • Author(s)
      山本英樹, 花木英明, 辻本育子, 金岩知之, 粟田ちひろ, 高尾敏文, 菊池章
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 翻訳後修飾によるWnt11の機能発現の制御2012

    • Author(s)
      山本英樹, 花木英明, 辻本育子, 粟田ちひろ, 高尾敏文, 菊池章
    • Organizer
      第85回日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] 翻訳後修飾によるWnt11蛋白質の機能発現の制御2012

    • Author(s)
      山本 英樹
    • Organizer
      生化学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 翻訳後修飾によるWnt蛋白質の機能発現の制御2011

    • Author(s)
      山本英樹, 粟田ちひろ, 高尾敏文, 岸田昭世, 岸田想子, 菊池章
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Final Research Report
  • [Presentation] 翻訳後修飾によるWnt蛋白質の機能発現の制御2011

    • Author(s)
      山本 英樹
    • Organizer
      生化学会
    • Place of Presentation
      京都国際会館(京都府)
    • Related Report
      2011 Research-status Report
  • [Presentation] 極性化された上皮細胞におけるWntの分泌制御機構

    • Author(s)
      山本 英樹, 花木 英明, 辻本 育子, 粟田 ちひろ, 高尾 敏文, 菊池 章
    • Organizer
      生化学会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Annual Research Report
  • [Book] 極性化上皮細胞におけるWnt分泌制御2013

    • Author(s)
      山本 英樹
    • Total Pages
      8
    • Publisher
      細胞工学(秀潤社)
    • Related Report
      2013 Annual Research Report
  • [Book] 極性化上皮細胞におけるWntの分泌制御2013

    • Author(s)
      山本 英樹、菊池 章
    • Total Pages
      8
    • Publisher
      秀潤社
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/

    • Related Report
      2013 Final Research Report
  • [Remarks] 大阪大学大学院医学系研究科分子病態生化学

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 大阪大学大学院医学系研究科分子病態生化学

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/

    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/pub/molbiobc/

    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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