Regulation of Wnt signaling by different endocytic pathway

• 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
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 分子病態学 / Wnt / Wntシグナル / Wnt5a / Wnt11 / Frizzled / エンドサイトーシス / クラスリン / Rac / Dkk1 / Frizzled受容体 / LRP6受容体

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] Wnt5a regulates distinct signalling pathways by binding to Frizzled2 (2010)
  • Author(s): Sato A., et al.
  • Journal Title: EMBO J. Volume: 29 Pages: 41-54
  • Peer Reviewed
• [Journal Article] LRP6 is internalized by Dkk1 to suppress its phosphorylation in the lipid raft and is recycled for reuse (2010)
  • Author(s): Sakane H., et al.
  • Journal Title: J.Cell Sci. Volume: 123 Pages: 360-368
  • Peer Reviewed
• [Journal Article] Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metalloproteinase (2010)
  • Author(s): Yamamoto, H., et al.
  • Journal Title: Oncogene Volume: 29 Pages: 2036-2046
  • Peer Reviewed
• [Journal Article] Wnt5a regulates distinct signalling pathways by binding to Frizzled2 (2010)
  • Author(s): Sato A., et al.
  • Journal Title: EMBO J. (in press)
  • 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., et al.
  • Journal Title: J. Cell Sci. (in press)
  • Peer Reviewed
• [Journal Article] Wnt5a signaling is involved in the aggressiveness of prostate cancer and expression of metallonroteinase (2010)
  • Author(s): Yamamoto H, et al.
  • Journal Title: Oncogene (in press)
  • 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
• [Journal Article] Laminin γ2 mediates Wnt5a-induced invasion of gastric cancer cells (2009)
  • Author(s): Yamamoto H, et al.
  • Journal Title: Gastroenterology 137 Pages: 242-252
  • Peer Reviewed
• [Journal Article] Selective activation mechanisms of Wnt signaling pathways (2009)
  • Author(s): Kikuchi A, et al.
  • Journal Title: Trends Cell Biol. 19 Pages: 119-129
  • Peer Reviewed
• [Presentation] Wnt5a-dependent activation of Rac through the internalization of Frizzled receptor (2010)
  • Author(s): 山本英樹
  • Organizer: 第33回日本分子生物学会年会 第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [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
• [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
  • Organizer: 日本化学会
  • Place of Presentation: 神戸ポートビプホテル(神戸市)
  • Year and Date: 2009-10-25
• [Presentation] クラスリンを介するエンドサイトーシスによるWnt5a依存性のRacの活性化 (2009)
  • Author(s): 山本英樹
  • Organizer: 日本癌学会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2009-10-03
• [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
• [Remarks] ホームページ等
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/molbiobc/