Alpha 6 beta 4 integrin regulates keratinocyte chemotaxis through differential GTPase activation and antagonism of alpha 3 beta 1 integrin.
J Cell Sci
; 116(Pt 17): 3543-56, 2003 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-12865436
ABSTRACT
Growth factor-induced cell migration and proliferation are essential for epithelial wound repair. Cell migration during wound repair also depends upon expression of laminin-5, a ligand for alpha 6 beta 4 integrin. We investigated the role of alpha 6 beta 4 integrin in laminin-5-dependent keratinocyte migration by re-expressing normal or attachment-defective beta 4 integrin in beta 4 integrin null keratinocytes. We found that expression of beta 4 integrin in either a ligand bound or ligand unbound state was necessary and sufficient for EGF-induced cell migration. In a ligand bound state, beta 4 integrin supported EGF-induced cell migration though sustained activation of Rac1. In the absence of alpha 6 beta 4 integrin ligation, Rac1 activation became tempered and EGF chemotaxis proceeded through an alternate mechanism that depended upon alpha 3 beta 1 integrin and was characterized by cell scattering. alpha 3 beta 1 integrin also relocalated from cell-cell contacts to sites of basal clustering where it displayed increased conformational activation. The aberrant distribution and activation of alpha 3 beta 1 integrin in attachment-defective beta 4 cells could be reversed by the activation of Rac1. Conversely, in WT beta 4 cells the normal cell-cell localization of alpha 3 beta 1 integrin became aberrant after the inhibition of Rac1. These studies indicate that the extracellular domain of beta 4 integrin, through its ability to bind ligand, functions to integrate the divergent effects of growth factors on the cytoskeleton and adhesion receptors so that coordinated keratinocyte migration can be achieved.
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Base de dados:
MEDLINE
Assunto principal:
Cicatrização
/
Queratinócitos
/
Quimiotaxia
/
Integrina alfa3beta1
/
Integrina alfa6beta4
Limite:
Humans
Idioma:
En
Revista:
J Cell Sci
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos