title: Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis.
abstract: Cellular adhesion is regulated by members of the cadherin family of adhesion receptors and their cytoplasmic adaptor proteins, the catenins. Adhesion complexes are regulated by recycling from the plasma membrane and proteolysis during apoptosis. We report that in MCF-7, MDA-MB-468 and MDCK cells, induction of apoptosis by agents that cause endoplasmic reticulum (ER) stress results in O-glycosylation of both beta-catenin and the E-cadherin cytoplasmic domain. O-glycosylation of newly synthesized E-cadherin blocks cell surface transport, resulting in reduced intercellular adhesion. O-glycosylated E-cadherin still binds to beta- and gamma-catenin, but not to p120-catenin. Although O-glycosylation can be inhibited with caspase inhibitors, cleavage of caspases associated with the ER or Golgi complex does not correlate with E-cadherin O-glycosylation. However, agents that induce apoptosis via mitochondria do not lead to E-cadherin O-glycosylation, and decrease adhesion more slowly. In MCF-7 cells, this is due to degradation of E-cadherin concomitant with cleavage of caspase-7 and its substrate poly(ADP-ribose) polymerase. We conclude that cytoplasmic O-glycosylation is a novel, rapid mechanism for regulating cell surface transport exploited to down-regulate adhesion in some but not all apoptosis pathways.
authors.affiliation: Department of Biochemistry, McMaster University, 1200 Main Street, West Hamilton, Ontario, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Zhu
authors.forename: B
authors.initials: B
authors.lastname: Leber
authors.forename: D W
authors.initials: DW
authors.lastname: Andrews
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism; D051177:Catenins; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051180:Desmoplakins; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D000095002:Delta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D004791:Enzyme Inhibitors; C495292:JUP protein, human; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D020169:Caspases; D000095002:Delta Catenin