title: Fibronectin rigidity response through Fyn and p130Cas recruitment to the leading edge.
abstract: Cell motility on extracellular matrices critically depends on matrix rigidity, which affects cell adhesion and formation of focal contacts. Receptor-like protein tyrosine phosphatase alpha (RPTPalpha) and the alphavbeta3 integrin form a rigidity-responsive complex at the leading edge. Here we show that the rigidity response through increased spreading and growth correlates with leading edge recruitment of Fyn, but not endogenous c-Src. Recruitment of Fyn requires the palmitoylation site near the N-terminus and addition of that site to c-Src enables it to support a rigidity response. In all cases, the rigidity response correlates with the recruitment of the Src family kinase to early adhesions. The stretch-activated substrate of Fyn and c-Src, p130Cas, is also required for a rigidity response and it is phosphorylated at the leading edge in a Fyn-dependent process. A possible mechanism for the fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement. With the greater displacement of Fyn from p130Cas on softer surfaces, there will be less phosphorylation. These studies emphasize the importance of force and nanometer-level movements in cell growth and function.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Kostic
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
mesh_terms: D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005353:Fibronectins / Q000502:physiology*; D017930:Genes, Reporter; D006801:Humans; D019308:Palmitic Acid / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D050719:Crk-Associated Substrate Protein; D005353:Fibronectins; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D019308:Palmitic Acid; C494957:FYN protein, human; D051076:Proto-Oncogene Proteins c-fyn; C516841:PTPRA protein, human; D017027:Protein Tyrosine Phosphatases; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4