The integrin alpha 7 cytoplasmic domain regulates cell migration, lamellipodia formation, and p130CAS/Crk coupling.
The integrin alpha(7)beta(1) is the major laminin-binding integrin in skeletal, heart, and smooth muscle and is a receptor for laminin-1 and -2. It mediates myoblast migration on laminin-1 and -2 and thus might be involved in muscle development and repair. Previously we have shown that alpha(7)B as well as the alpha(7)A and -C splice variants induce cell motility on laminin when transfected into nonmotile HEK293 cells. In this study we have investigated the role of the cytoplasmic domain of alpha(7) in the laminin-induced signal transduction of alpha(7)beta(1) integrin regulating cell adhesion and migration. Deletion of the cytoplasmic domain did not affect assembly of the mutated alpha(7)Deltacyt/beta(1) heterodimer on the cell surface or adhesion of alpha(7)Deltacyt-transfected cells to laminin. The motility of these cells on the laminin-1/E8 fragment, however, was significantly reduced to the level of mock-transfected cells; lamellipodia formation and polarization of the cells were also impaired. Adhesion to the laminin-1/E8 fragment induced tyrosine phosphorylation of the focal adhesion kinase, paxillin, and p130(CAS) as well as the formation of a p130(CAS)-Crk complex in wild-type alpha(7)B-transfected cells. In alpha(7)BDeltacyt cells, however, the extent of p130(CAS) tyrosine formation was reduced and formation of the p130(CAS)-Crk complex was impaired, with unaltered levels of p130(CAS) and Crk protein levels. These findings indicate adhesion-dependent regulation of p130(CAS)/Crk complex formation by the cytoplasmic domain of alpha(7)B integrin after cell adhesion to laminin-1/E8 and imply alpha(7)B-controlled lamellipodia formation and cell migration through the p130(CAS)/Crk protein complex.
Mielenz
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Klinisch-molekular biologisches Forschungszentrum, Department for Experimental Medicine I, University of Erlangen-Nürnberg, Glückstrasse 6, 91054 Erlangen, Germany.
Hapke
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Pöschl
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von Der Mark
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von Der Mark
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D015703:Antigens, CD / Q000737:chemistry* / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity; D003593:Cytoplasm / Q000502:physiology; D019281:Dimerization; D006801:Humans; D039001:Integrin alpha Chains; D007797:Laminin / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D011554:Pseudopodia / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D014162:Transfection; D044767:Ubiquitin-Protein Ligases
D015703:Antigens, CD; D039001:Integrin alpha Chains; D007797:Laminin; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; C085725:integrin alpha7; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; C067419:CBL protein, human