title: Microtubules Inhibit E-Cadherin Adhesive Activity by Maintaining Phosphorylated p120-Catenin in a Colon Carcinoma Cell Model.
abstract: Tight regulation of cadherin-mediated intercellular adhesions is critical to both tissue morphogenesis during development and tissue homeostasis in adults. Cell surface expression of the cadherin-catenin complex is often directly correlated with the level of adhesion, however, examples exist where cadherin appears to be inactive and cells are completely non-adhesive. The state of p120-catenin phosphorylation has been implicated in regulating the adhesive activity of E-cadherin but the mechanism is currently unclear. We have found that destabilization of the microtubule cytoskeleton, independent of microtubule plus-end dynamics, dephosphorylates p120-catenin and activates E-cadherin adhesion in Colo 205 cells. Through chemical screening, we have also identified several kinases as potential regulators of E-cadherin adhesive activity. Analysis of several p120-catenin phosphomutants suggests that gross dephosphorylation of p120-catenin rather than that of specific amino acids may trigger E-cadherin adhesion. Uncoupling p120-catenin binding to E-cadherin at the membrane causes constitutive adhesion in Colo 205 cells, further supporting an inhibitory role of phosphorylated p120-catenin on E-cadherin activity.
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.|Department of Biology, Truman State University, Kirksville, Missouri, United States of America.
authors: Stephanie L
authors: SL
authors: Maiden
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.
authors: Yuliya I
authors: YI
authors: Petrova
authors: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America.|Seattle Children's Research Institute and University of Washington School of Medicine, Seattle, Washington, United States of America.
authors: Barry M
authors: BM
authors: Gumbiner
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D017346:Protein Serine-Threonine Kinases; D000095002:Delta Catenin; C000722347:CTNND1 protein, human