Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization.

Kagermeier-Schenk B, Wehner D, Oezhan-Kizil G, Yamamoto H, Li J, Kirchner K, Hoffmann C, Stern P, Kikuchi A, Schambony A, Weidinger G (2011)

Publication Type: Journal article, Original article

Subtype: other

Publication year: 2011

Journal

Developmental Cell Elsevier (Cell Press)

Publisher: Elsevier Inc.

Book Volume: 21

Pages Range: 1129-1143

Journal Issue: 6

URI: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22100263&retmode=ref&cmd=prlinks

DOI: 10.1016/j.devcel.2011.10.015

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.

Authors with CRIS profile

Katharina Kirchner Lehrstuhl für Entwicklungsbiologie (Ebio) Alexandra Schambony Lehrstuhl für Entwicklungsbiologie (Ebio)

Involved external institutions

Technische Universität Dresden DE Germany (DE) Osaka University / 大阪大学 JP Japan (JP) University of Manchester GB United Kingdom (GB)

How to cite

APA:

Kagermeier-Schenk, B., Wehner, D., Oezhan-Kizil, G., Yamamoto, H., Li, J., Kirchner, K.,... Weidinger, G. (2011). Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization. Developmental Cell, 21(6), 1129-1143. https://doi.org/10.1016/j.devcel.2011.10.015

MLA:

Kagermeier-Schenk, Birgit, et al. "Waif1/5T4 inhibits Wnt/β-catenin signaling and activates noncanonical Wnt pathways by modifying LRP6 subcellular localization." Developmental Cell 21.6 (2011): 1129-1143.

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