| First Author | Saito-Diaz K | Year | 2018 |
| Journal | Dev Cell | Volume | 44 |
| Issue | 5 | Pages | 566-581.e8 |
| PubMed ID | 29533772 | Mgi Jnum | J:347406 |
| Mgi Id | MGI:6191895 | Doi | 10.1016/j.devcel.2018.02.013 |
| Citation | Saito-Diaz K, et al. (2018) APC Inhibits Ligand-Independent Wnt Signaling by the Clathrin Endocytic Pathway. Dev Cell 44(5):566-581.e8 |
| abstractText | Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting beta-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased beta-catenin levels. In contrast, APC2 loss does not promote receptor activation. We show that APC exists in a complex with clathrin and that Wnt pathway activation in APC-deficient cells requires clathrin-mediated endocytosis. Finally, we demonstrate conservation of this mechanism in Drosophila intestinal stem cells. We propose a model in which APC and APC2 function to promote beta-catenin degradation, and APC also acts as a molecular "gatekeeper" to block receptor activation via the clathrin pathway. |
