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Published online 16 October 2006. doi:10.1083/jcb.200606050
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 2, 271-281
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Article

Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes

Christina Wasmeier1, Maryse Romao2, Lynn Plowright3, Dorothy C. Bennett3, Graça Raposo2, and Miguel C. Seabra1

1 Molecular and Cellular Medicine, Division of Biomedical Sciences, Imperial College London, London SW7 2AZ, England, UK
2 Institut Curie, Centre National de la Recherche Scientifique, UMR144, Paris, Cedex 75005, France
3 Department of Basic Medical Sciences, St George's University of London, London SW17 0RE, England, UK

Correspondence to Miguel C. Seabra: m.seabra{at}imperial.ac.uk

Amutation in the small GTPase Rab38 gives rise to the mouse coat color phenotype "chocolate" (cht), implicating Rab38 in the regulation of melanogenesis. However, its role remains poorly characterized. We report that cht Rab38G19V is inactive and that the nearly normal pigmentation in cht melanocytes results from functional compensation by the closely related Rab32. In cht cells treated with Rab32-specific small interfering RNA, a dramatic loss of pigmentation is observed. In addition to mature melanosomes, Rab38 and Rab32 localize to perinuclear vesicles carrying tyrosinase and tyrosinase-related protein 1, consistent with a role in the intracellular sorting of these proteins. In Rab38/Rab32-deficient cells, tyrosinase appears to be mistargeted and degraded after exit from the trans-Golgi network (TGN). This suggests that Rab38 and Rab32 regulate a critical step in the trafficking of melanogenic enzymes, in particular, tyrosinase, from the TGN to melanosomes. This work identifies a key role for the Rab38/Rab32 subfamily of Rab proteins in the biogenesis of melanosomes and potentially other lysosome-related organelles.

Abbreviations used in this paper: AP-3, adaptor protein 3; BLOC, biogenesis of lysosome-related organelles complex; HPS, Hermansky-Pudlak syndrome; IF, immunofluorescence; LRO, lysosome-related organelle; Tyrp1, tyrosinase-related protein 1.


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