Integrins stimulate E-cadherin-mediated intercellular adhesion by regulating Src-kinase activation and actomyosin contractility.
Cadherins and integrins are major adhesion molecules regulating cell-cell and cell-matrix interactions. In vitro and in vivo studies have demonstrated the existence of crosstalk between integrins and cadherins in cell adhesion and motility. We used a dual pipette assay to measure the force required to separate E-cadherin-producing cell doublets and to investigate the role of integrin in regulating the strength of intercellular adhesion. A greater force was required to separate cell doublets bound to fibronectin or vitronectin-coated beads than for doublets bound to polylysine-coated beads. This effect depended on cell spreading and the duration of stimulation. Cells expressing type II cadherin-7 also responded to fibronectin stimulation to produce a higher intercellular adhesion. Establishment of cadherin-mediated adhesion needed ROCK, MLCK and myosin ATPase II activity. The regulation of intercellular adhesion strength by integrin stimulation required activation of Src family kinases, ROCK and actomyosin contractility. These findings highlight the importance and mechanisms of molecular crosstalk between cadherins and integrins in the control of cell plasticity during histogenesis and morphogenesis.
Martinez-Rico
Clara
C
UMR144 CNRS-Institut Curie, 75248 Paris Cedex 05, France.
Pincet
Frederic
F
Thiery
Jean-Paul
JP
Dufour
Sylvie
S
D000205:Actomyosin / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002645:Chickens; D005434:Flow Cytometry; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016608:Talin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
D000577:Amides; D015820:Cadherins; D039081:Integrin alpha5beta1; D016023:Integrins; D011725:Pyridines; D016608:Talin; C108830:Y 27632; D000205:Actomyosin; D019061:src-Family Kinases