CCN3 controls 3D spatial localization of melanocytes in the human skin through DDR1.
J Cell Biol
; 175(4): 563-9, 2006 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-17101694
ABSTRACT
Melanocytes reside within the basal layer of the human epidermis, where they attach to the basement membrane and replicate at a rate proportionate to that of keratinocytes, maintaining a lifelong stable ratio. In this study, we report that coculturing melanocytes with keratinocytes up-regulated CCN3, a matricellular protein that we subsequently found to be critical for the spatial localization of melanocytes to the basement membrane. CCN3 knockdown cells were dissociated either upward to the suprabasal layers of the epidermis or downward into the dermis. The overexpression of CCN3 increased adhesion to collagen type IV, the major component of the basement membrane. As the receptor responsible for CCN3-mediated melanocyte localization, we identified discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase that acts as a collagen IV adhesion receptor. DDR1 knockdown decreased melanocyte adhesion to collagen IV and shifted melanocyte localization in a manner similar to CCN3 knockdown. These results demonstrate an intricate and necessary communication between keratinocytes and melanocytes in maintaining normal epidermal homeostasis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Movimento Celular
/
Receptores Proteína Tirosina Quinases
/
Proteínas Imediatamente Precoces
/
Peptídeos e Proteínas de Sinalização Intercelular
/
Melanócitos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos