Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis

Cellular adhesion is regulated by members of the cadherin family of adhesio n receptors and their cytoplasmic adaptor proteins, the catenins. Adhesion complexes are regulated by recycling from the plasma membrane and proteolys is during apoptosis. We report that in MCF-7, MDA-MB-468 and MDCK cells, in duction of apoptosis by agents that cause endoplasmic reticulum (ER) stress results in O-glycosylation of both beta -catenin and the E-cadherin cytopl asmic domain. O-glycosylation of newly synthesized E-cadherin blocks cell s urface transport, resulting in reduced intercellular adhesion. O-glycosylat ed E-cadherin still binds to beta- and gamma -catenin, but not to p120-cate nin. Although O-glycosylation can be inhibited with caspase inhibitors, cle avage of caspases associated with the ER or Golgi complex does not correlat e with E-cadherinO-glycosylation. However, agents that induce apoptosis via mitochondria do not lead to E-cadherin O-glycosylation, and decrease adhes ion more slowly. In MCF-7 cells, this is due to degradation of E-cadherin c oncomitant with cleavage of caspase-7 and its substrate poly(ADP-ribose) po lymerase. We conclude that cytoplasmic O-glycosylation is a novel, rapid me chanism for regulating cell surface transport exploited to down-regulate ad hesion in some but not all apoptosis pathways.