Traffic control: p120-catenin acts as a gatekeeper to control the fate of classical cadherins in mammalian cells

Abstract

Proteins of the p120 family have been implicated in the regulation of cadherin-based cell adhesion, but their relative importance in this process and their mechanism of action have remained less clear. Three papers in this issue suggest that p120 plays a key role in maintaining normal levels of cadherin in mammalian cells, and that it may do so by regulating cadherin trafficking (Chen et al., 2003; Davis et al., 2003; Xiao et al., 2003).

Figure 1.

The cellular itinerary and fate of classical cadherins. (A) Adherens junctions are assembled around classic cadherins. Their extracellular domains mediate homophilic cell–cell adhesion. The distal regions of their cytoplasmic tails bind β-catenin, which in turn binds α-catenin. α -catenin links the junction to the actin cytoskeleton via direct and indirect interactions. The juxtamembrane domain of the cadherin cytoplasmic tail binds proteins of the p120 family. (B) The surface expression of E-cadherin is one facet of a complex trafficking network. Upon delivery to the cell surface, classical cadherins may adopt either of two fates. Productive homophilic ligation and attachment to the cytoskeleton allows cadherins to be retained at the cell surface, supporting lateral clustering and assembly of cadherins into adherens junctions (red arrow). Alternatively, cadherins may be endocytosed. They then can either be trafficked back to the cell surface (via a post-Golgi recycling pathway) or ultimately targeted for degradation, at least in part via lysosomes. Cadherins delivered to the cell surface can thus derive either from newly synthesized material or via the recycling pathway. p120 appears to play a key gatekeeper function in determining the fate of cadherins after delivery to the surface. When incorporated into the cadherin complex p120 can also potentially coordinate a range of other activities, including surface adhesion, cadherin clustering, and cell signaling.