The ocular albinism type 1 (OA1) G-protein-coupled receptor functions with MART-1 at early stages of melanogenesis to control melanosome identity and composition.
Hum Mol Genet
; 18(23): 4530-45, 2009 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-19717472
ABSTRACT
OA1 (GPR143; GPCR, G-protein-coupled receptor), the protein product of the ocular albinism type 1 gene, encodes a pigment-cell-specific GPCR that localizes intracellularly to melanosomes. OA1 mutations result in ocular albinism due to alterations in melanosome formation, suggesting that OA1 is a key player in the biogenesis of melanosomes. To address the function of OA1 in melanosome biogenesis, we have used siRNA inactivation and combined morphological and biochemical methods to investigate melanosome ultrastructure, melanosomal protein localization and expression in human pigmented melanocytic cells. OA1 loss of function leads to decreased pigmentation and causes formation of enlarged aberrant premelanosomes harboring disorganized fibrillar structures and displaying proteins of mature melanosomes and lysosomes at their membrane. Moreover, we show that OA1 interacts biochemically with the premelanosomal protein MART-1. Inactivation of MART-1 by siRNA leads to a decreased stability of OA1 and is accompanied by similar defects in premelanosome biogenesis and composition. These data show for the first time that melanosome composition and identity are regulated at early stages by OA1 and that MART-1 likely acts as an escort protein for this GPCR.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Retina
/
Glicoproteínas de Membrana
/
Melanosomas
/
Receptores Acoplados a Proteínas G
/
Proteínas del Ojo
/
Melanocitos
/
Antígenos de Neoplasias
/
Proteínas de Neoplasias
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article