| The Wnt signaling pathway regulates many diverse processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation, and has also been implicated in a number of cancers, bone density maintenance, and neurological conditions during adulthood. While numerous Wnts, their cognate receptors of the Frizzled and Arrow/LRP5/6 families, and downstream pathway components have been identified, little is known about the initial events occurring directly after receptor activation. We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. Blockade of clathrin-mediated endocytosis abolishes the internalization of Wnt, as well as Wnt-stimulated accumulation of beta-catenin and target gene expression. As internalized Wnts transit partially through the transferrin recycling pathway, it is possible that a "signaling endosome" serves as a nexus for activated Wnt pathway components. |
