| Literature DB >> 22100263 |
Birgit Kagermeier-Schenk1, Daniel Wehner, Günes Ozhan-Kizil, Hideki Yamamoto, Jian Li, Katharina Kirchner, Christian Hoffmann, Peter Stern, Akira Kikuchi, Alexandra Schambony, Gilbert Weidinger.
Abstract
Wnt proteins can activate distinct signaling pathways, but little is known about the mechanisms regulating pathway selection. Here we show that the metastasis-associated transmembrane protein Wnt-activated inhibitory factor 1 (Waif1/5T4) interferes with Wnt/β-catenin signaling and concomitantly activates noncanonical Wnt pathways. Waif1 inhibits β-catenin signaling in zebrafish and Xenopus embryos as well as in mammalian cells, and zebrafish waif1a acts as a direct feedback inhibitor of wnt8-mediated mesoderm and neuroectoderm patterning during zebrafish gastrulation. Waif1a binds to the Wnt coreceptor LRP6 and inhibits Wnt-induced LRP6 internalization into endocytic vesicles, a process that is required for pathway activation. Thus, Waif1a modifies Wnt/β-catenin signaling by regulating LRP6 subcellular localization. In addition, Waif1a enhances β-catenin-independent Wnt signaling in zebrafish embryos and Xenopus explants by promoting a noncanonical function of Dickkopf1. These results suggest that Waif1 modulates pathway selection in Wnt-receiving cells.Entities:
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Year: 2011 PMID： 22100263 DOI： 10.1016/j.devcel.2011.10.015
Source DB: PubMed Journal: Dev Cell ISSN： 1534-5807 Impact factor: 12.270