RPTP-alpha acts as a transducer of mechanical force on alphav/beta3-integrin-cytoskeleton linkages.
Cell motility on ECM critically depends on the cellular response to force from the matrix. We find that force-dependent reinforcement of alphav/beta3-integrin-mediated cell-matrix connections requires the receptor-like tyrosine phosphatase alpha (RPTPalpha). RPTPalpha colocalizes with alphav-integrins at the leading edge during early spreading, and coimmunoprecipitates with alphav-integrins during spreading on fibronectin and vitronectin. RPTPalpha-dependent activation of Src family kinases, in particular activation of Fyn, is required for the force-dependent formation of focal complexes and strengthening of alphav/beta3-integrin-cytoskeleton connections during the initial phase of ECM contact. These observations indicate that Src family kinases have distinct functions during adhesion site assembly, and that RPTPalpha is an early component in force-dependent signal transduction pathways leading to the assembly of focal complexes on both fibronectin and vitronectin.
von Wichert
Gotz
G
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Jiang
Guoying
G
Kostic
Ana
A
De Vos
Kurt
K
Sap
Jan
J
Sheetz
Michael P
MP
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D005353:Fibronectins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D022001:Focal Adhesions / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4; D011956:Receptors, Cell Surface; D015398:Signal Transduction / Q000235:genetics; D013314:Stress, Mechanical; D014746:Vimentin / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D005353:Fibronectins; D039302:Integrin alphaVbeta3; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D014746:Vimentin; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases; C516843:Ptpra protein, mouse; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4