Regulation of Wnt signaling by different endocytic pathway

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790320
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: Osaka University (2010); Hiroshima University (2009)
• Principal Investigator: YAMAMOTO Hideki Osaka University, 医学系研究科, 准教授 (20372691)
• Project Period (FY): 2009 – 2010
• Keywords: 分子病態学 / Wnt

Research Abstract

We examined whether the internalization of Wnt receptors affects the ability of Dkk1 and Wnt5a to regulate Wnt signaling pathways. A secreted protein Dkk1, which acts as an inhibitor of Wnt signaling, reduced the amount of LRP6 from the lipid raft and induced clathrin-mediated internalization of LRP6 to suppress β-catenin pathway. Wnt5a activated Rac in the β-catenin-independent pathway, and Frizzled 2 (Fz2), clathrin, arrestin, and Ror1 or Ror2 were required for this action. These results indicate that Wnt signaling pathway is regulated by the internalization of Wnt receptors.

Research Products

• [Journal Article] Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase. (2010)
  • Author(s): Yamamoto, H., Oue, N., Sato, A., Hasegawa, Y., Yamamoto, H., Matsubara, A., Yasui, W., Kikuchi, A.
  • Journal Title: Oncogene 29 Pages: 2036-2046
  • Peer Reviewed
• [Journal Article] LRP6 is internalized by Dkkl to suppress its phosphorylation in the lipid raft and is recycled for reuse. (2010)
  • Author(s): Sakane, H., Yamamoto, H., Kikuchi, A.
  • Journal Title: J.Cell Sci. 123 Pages: 360-368
  • Peer Reviewed
• [Journal Article] Wnt5a regulates distinct signaling pathways by binding to Frizzled2. (2010)
  • Author(s): Sato, A.,Yamamoto, H.,Sakane, H., Koyama, H., Kikuchi, A.
  • Journal Title: EMBO J. 29 Pages: 41-54
  • Peer Reviewed
• [Journal Article] Laminin・2 mediates Wnt5a-induced invasion of Gastric Cancer Cells. (2009)
  • Author(s): Yamamoto, H.,Kitadai, Y.,Yamamoto, H., Oue, N., Ohdan, H., Yasui, W., Kikuchi, A.
  • Journal Title: Gastroenterology 137 Pages: 242-252
  • Peer Reviewed
• [Journal Article] Selective activation of mechanisms of Wnt signaling pathways. (2009)
  • Author(s): Kikuchi, A.,Yamamoto, H.,and Sato, A.
  • Journal Title: Trends Cell Biol. 19 Pages: 119-129
  • Peer Reviewed
• [Presentation] Wnt5a-dependent activation of Rac throug the internalization of Frizzled receptor (2010)
  • Author(s): 山本英樹、佐藤朗、坂根洋、菊池章
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-20101210
• [Presentation] 異なる受容体エンドサイトーシス経路を介するWntシグナル伝達の制御機構 (2009)
  • Author(s): 山本英樹、坂根洋、菊池章
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20091021-20091024
• [Remarks] ホームページ等
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/