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J Cell Biol ; 199(2): 347-63, 2012 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-23071155

RESUMEN

During keratinocyte differentiation and stratification, cells undergo extensive remodeling of their actin cytoskeleton, which is important to control cell mobility and to coordinate and stabilize adhesive structures necessary for functional epithelia. Limited knowledge exists on how the actin cytoskeleton is remodeled in epithelial stratification and whether cell shape is a key determinant to trigger terminal differentiation. In this paper, using human keratinocytes and mouse epidermis as models, we implicate miR-24 in actin adhesion dynamics and demonstrate that miR-24 directly controls actin cable formation and cell mobility. miR-24 overexpression in proliferating cells was sufficient to trigger keratinocyte differentiation both in vitro and in vivo and directly repressed cytoskeletal modulators (PAK4, Tks5, and ArhGAP19). Silencing of these targets recapitulated the effects of miR-24 overexpression. Our results uncover a new regulatory pathway involving a differentiation-promoting microribonucleic acid that regulates actin adhesion dynamics in human and mouse epidermis.


Asunto(s)
Citoesqueleto de Actina/metabolismo , MicroARNs/metabolismo , Animales , Adhesión Celular/genética , Diferenciación Celular/genética , Movimiento Celular/genética , Proliferación Celular , Células Cultivadas , Epidermis/metabolismo , Proteínas Activadoras de GTPasa , Humanos , Queratinocitos/metabolismo , Ratones , Ratones Transgénicos , MicroARNs/genética , Proteínas de Unión a Fosfato , Fosfoproteínas , Interferencia de ARN , ARN Interferente Pequeño , Quinasas p21 Activadas
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