Canonical Wnt signaling induces focal adhesion and Integrin beta-1 endocytosis
Nydia Tejeda-Muñoz,
Marco Morselli,
Yuki Moriyama,
Pooja Sheladiya,
Matteo Pellegrini,
Edward M. De Robertis
Affiliations
Nydia Tejeda-Muñoz
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA; Corresponding author
Marco Morselli
Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, University of Parma, Parm, Italy
Yuki Moriyama
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA; JT Biohistory Research Hall, Osaka, Japan and Chuo University, Faculty of Science and Engineering, Tokyo, Japan
Pooja Sheladiya
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA
Matteo Pellegrini
Department of Molecular, Cellular and Developmental Biology, University of California, Los Angeles, CA 90095-1662, USA
Edward M. De Robertis
Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles 90095-1662, USA; Corresponding author
Summary: During canonical Wnt signaling, the Wnt receptor complex is sequestered together with glycogen synthase kinase 3 (GSK3) and Axin inside late endosomes, known as multivesicular bodies (MVBs). Here, we present experiments showing that Wnt causes the endocytosis of focal adhesion (FA) proteins and depletion of Integrin β 1 (ITGβ1) from the cell surface. FAs and integrins link the cytoskeleton to the extracellular matrix. Wnt-induced endocytosis caused ITGβ1 depletion from the plasma membrane and was accompanied by striking changes in the actin cytoskeleton. In situ protease protection assays in cultured cells showed that ITGβ1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and FA-associated proteins. An in vivo model using Xenopus embryos dorsalized by Wnt8 mRNA showed that ITGβ1 depletion decreased Wnt signaling. The finding of a crosstalk between two major signaling pathways, canonical Wnt and focal adhesions, should be relevant to human cancer and cell biology
