Regulation of Wnt signaling by different endocytic pathway

我们研究了Wnt受体的内化是否会影响Dkk1和Wnt5a调节Wnt信号通路的能力。分泌蛋白Dkk1作为Wnt信号的抑制剂，减少脂质筏中LRP6的数量，诱导网格蛋白介导的LRP6内化，抑制β-catenin通路。Wnt5a在β-catenin-independent通路上激活Rac，而Frizzled 2 （Fz2）、网格蛋白、捕集蛋白和Ror1或Ror2是这一作用所必需的。这些结果表明，Wnt信号通路受Wnt受体内化的调控。

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.