Figure 9.

p120 regulates clathrin-dependent endocytosis of VE-cadherin. Similar to other classical cadherins, VE-cadherin associates with the catenins and assembles into intercellular junctions. A pool of VE-cadherin may also be present outside of the junctions at the plasma membrane. On endocytosis, p120 dissociates from the VE-cadherin tail. The loss of p120 is predicted to expose sequence motifs on the cadherin cytoplasmic domain that mediate association with adaptor proteins involved in clathrin-dependent internalization, such as AP-2. Regardless of the precise mechanism, p120 functions to regulate plasma membrane levels of cadherins by regulating internalization from the plasma membrane. The model reveals a unique molecular mechanism by which a cytoplasmic protein, in this case p120, selectively regulates clathrin mediated endocytosis of a transmembrane receptor.