Canonical Wnt Signaling Induces Focal Adhesion and Integrin Beta-1 Endocytosis

During canonical Wnt signaling, the Lrp6 and Frizzled co-receptors bind to the Wnt growth factor and the complex is endocytosed and sequestered together with Glycogen Synthase Kinase 3 (GSK3), Dishevelled (Dvl), and Axin inside the intraluminal vesicles of 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 mayor signaling pathways, canonical Wnt and focal adhesions, should be relevant to human cancer and cell biology.