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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Cytoplasmic O-glycosylation prevents cell surface transport of E-cadherin during apoptosis. 1168 40

Adhesions of cells to extracellular matrix and adjacent cells are mediated by integrins and VE-cadherin, respectively. Although these adhesion processes play crucial roles in vascular cell migration and angiogenesis, it remains unclear as to how they are coordinated to regulate cellular functions. We report here that integrin engagement by treating bovine endothelial aortic cell monolayers with beads coated with fibronectin (Fn) led to disruption of the VE-cadherin-containing adherens junctions. This disruption was accompanied by increases of tyrosine phosphorylation of beta-catenin, gamma-catenin, and p120ctn, as well as the dissociation of alpha-catenin and gamma-catenin from VE-cadherin. We applied a membrane-targeted Src reporter based on the fluorescence resonance energy transfer technique to visualize the dynamic Src activation at subcellular levels in live cells. The integrin engagement induced by Fn-coated beads caused the activation of Src around the beads and at adherens junctions, which are subsequently disrupted. The inhibition of Src with PP1 blocked the effects of integrin engagement on adherens junctions. Although Ras can also modulate adherens junctions, the resulting patterns of phosphorylation and association of junction proteins were distinct from those induced by integrin engagement. The inhibition of Ras by RasN17 did not rescue the disruption of adherens junctions induced by integrin engagement or by Src activation. Integrin engagement by Fn-coated beads also induced a significant alteration of cortical actin filaments at adherens junctions. The results indicate that integrin engagement disrupts VE-cadherin-containing adherens junctions via the activation of Src, but not Ras, possibly as a result of modulation of the actin network.
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PMID:Integrins regulate VE-cadherin and catenins: dependence of this regulation on Src, but not on Ras. 1644 27