In theory, the absence of cadherins in p120-deficient cells indicates either a failure to normally synthesize cadherins or an efficient means of eliminating them when p120 is not present. However, our pulse-chase data indicate that p120 is not required for normal synthesis or transit of cadherin to the cell surface. Instead, p120 absence dramatically accelerates cadherin degradation after its arrival at the surface, indicating a role in regulating cadherin turnover at the membrane (modeled in Fig. 7). Our data do not precisely distinguish the point at which p120 acts to prevent degradation. The simplest explanation is that p120 limits degradation by regulating internalization. Only cadherin-bound p120 is phosphorylated (Thoreson et al., 2000), and p120 phosphorylation is the most likely means of regulating p120–cadherin affinity and/or p120 activity in the complex. We cannot rule out the less likely possibility that once internalized, p120 might control the next step, which targets the endocytosed cadherin for either degradation or recycling back to the surface. Regardless, it is likely that the ultimate destruction of the cadherin in p120-deficient A431 cells resides mainly in the proteosome, and to some extent in the lysosome.
