A critical role for endocytosis in Wnt signaling.
Submitted by admin on Thu, 10/14/2010 - 22:44
| Title | A critical role for endocytosis in Wnt signaling. |
| Publication Type | Journal Article |
| Year of Publication | 2006 |
| Authors | Blitzer JT, Nusse R |
| Journal | BMC Cell Biol |
| Volume | 7 |
| Pagination | 28 |
| ISSN | 1471-2121 (Electronic); 1471-2121 (Linking) |
| Abstract | BACKGROUND: The Wnt signaling pathway regulates many processes during embryonic development, including axis specification, organogenesis, angiogenesis, and stem cell proliferation. Wnt signaling 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. RESULTS: We show here that Wnt proteins are rapidly endocytosed by a clathrin- and dynamin-mediated process. While endocytosis has traditionally been considered a principal mechanism for receptor down-regulation and termination of signaling pathways, we demonstrate that interfering with clathrin-mediated endocytosis actually blocks Wnt signaling at the level of beta-catenin accumulation and target gene expression. CONCLUSION: A necessary component of Wnt signaling occurs in a subcellular compartment distinct from the plasma membrane. Moreover, 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. |
| DOI | 10.1186/1471-2121-7-28 |
