XXXX inhibits endocytosis of cadherin dimers.

@entity16854 @entity8780 @entity3545
UNASSIGNED: Dynamic regulation of endothelial cell adhesion is central to vascular development and maintenance. Furthermore, altered endothelial adhesion is implicated in numerous diseases. Thus, normal vascular patterning and maintenance require tight regulation of endothelial cell adhesion dynamics. Yet, the mechanisms that control junctional plasticity are not fully understood. @entity3545 is an adhesive protein found in adherens junctions of endothelial cells. @entity3545 mediates adhesion through trans interactions formed by its extracellular domain. Trans binding is followed by cis interactions that laterally cluster the cadherin in junctions. @entity3545 is linked to the actin cytoskeleton through cytoplasmic interactions with b and a-catenin, which serve to increase adhesive strength. Furthermore, @entity8780 binds to the cytoplasmic tail of the cadherin and stabilizes it at the plasma membrane. Here, we report that induced cis-dimerization of @entity3545 inhibits endocytosis independent of both @entity8780 binding and trans interactions. However, we find that @entity16854 , a protein that links membrane proteins to the spectrin-actin cytoskeleton, associates with @entity3545 and inhibits its endocytosis. @entity16854 inhibits @entity3545 endocytosis independent of @entity8780 binding. We propose a model in which @entity16854 associates with and inhibits the endocytosis of @entity3545 cis-dimers. Our findings support a novel mechanism for regulation of @entity3545 endocytosis through ankyrin association with cadherin engaged in lateral interactions.
