Selective activation mechanisms of Wnt signaling pathways

Wnts comprise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms, including cellular proliferation, differentiation, migration and polarity. Wnts have many receptors that are present on a variety of cell types, partly specifying which Wnt pathways are activated. Recently, evidence has been accumulating that specificity of activation downstream of Wnt is also regulated by receptor-mediated endocytosis and the presence of cofactors such as heparan sulfate proteoglycans, in addition to the formation of specific ligand-receptor pairs. Here, we describe how the different endocytic routes of Wnt receptors through caveolin and clathrin determine specificity of Wnt signaling in vertebrates.