Skip Navigation


Human Molecular Genetics Advance Access originally published online on August 28, 2009
Human Molecular Genetics 2009 18(23):4530-4545; doi:10.1093/hmg/ddp415
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
18/23/4530    most recent
ddp415v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Giordano, F.
Right arrow Articles by Raposo, G.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giordano, F.
Right arrow Articles by Raposo, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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

Francesca Giordano1,2, Ciro Bonetti3, Enrico M. Surace3, Valeria Marigo4,* and Graça Raposo1,2,*

1 Institut Curie, Centre de Recherche, Paris F-75248, France, 2 Structure and Membrane Compartments CNRS, UMR144, Paris F-75248, France, 3 Telethon Institute of Genetics and Medicine, TIGEM, Naples, Italy and 4 Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy

* To whom correspondence should be addressed. Tel: +33 156246441; Fax: +33 156246421; Email: graposo{at}curie.fr (G.R.); Tel: +39 592055392; Fax: +39 592055410; Email: valeria.marigo{at}unimore.it (V.M)

Received July 7, 2009; Accepted August 25, 2009

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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.