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Cytoplasmic O ‐glycosylation prevents cell surface transport of E‐cadherin during apoptosis
Author(s) -
Zhu Weijia,
Leber Brian,
Andrews David W.
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.21.5999
Subject(s) - microbiology and biotechnology , biology , cadherin , endoplasmic reticulum , glycosylation , cell adhesion , catenin , golgi apparatus , apoptosis , cytoplasm , n linked glycosylation , biochemistry , signal transduction , cell , glycan , glycoprotein , wnt signaling pathway
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 β‐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 β‐ and γ‐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.