“…Lastly, evidence that endocytosis appears to be an obligate step for Wnt signal transduction (Bilic et al, 2007; Blitzer & Nusse, 2006), as is known for many other signaling pathways (Goh & Sorkin, 2013; Haglund & Dikic, 2012), raises the possibility that cadherins may impact Wnt signaling by controlling Wnt receptor complex internalization into signalosomes (Bilic et al, 2007). In this regard, recent studies show that Wnt receptor complex activation can promote the sequestration of GSK3 into multivesicular bodies (Taelman et al, 2010) (although perhaps not in flies; Gagliardi, Hernandez, McGough, & Vincent, 2014), leading to β-catenin stabilization and signaling, where the cadherin and p120 ctn appear required for this process (Vinyoles et al, 2014). Given that the cadherin/catenin complex is fundamental not only for cell–cell adhesion but for basic membrane dynamics (Abreu-Blanco, Verboon, Liu, Watts, & Parkhurst, 2012; Schepis, Sepich, & Nelson, 2012), it may not be surprising to find these examples of the cadherin/catenin complex being both required for and inhibitory to Wnt/β-catenin signaling.…”