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Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes.

Wasmeier, C; Romao, M; Plowright, L; Bennett, DC; Raposo, G; Seabra, MC (2006) Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. The Journal of Cell Biology, 175 (2). pp. 271-281. ISSN 1540-8140
SGUL Authors: Bennett, Dorothy Catherine

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A mutation 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 Rab38(G19V) 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.

Item Type: Article
Additional Information: © The Rockefeller University Press. Full text made available here as publisher permits third parties to use their published materials under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License six months after publication.
Keywords: Animals, Cells, Cultured, Golgi Apparatus, Humans, Immunoblotting, Lentivirus, Melanins, Melanosomes, Membrane Glycoproteins, Mice, Mice, Inbred C57BL, Monophenol Monooxygenase, Mutation, Oxidoreductases, Protein Transport, RNA, Small Interfering, Rats, Subcellular Fractions, rab GTP-Binding Proteins, trans-Golgi Network, Science & Technology, Life Sciences & Biomedicine, Cell Biology, CELL BIOLOGY, HERMANSKY-PUDLAK-SYNDROME, LYSOSOME-RELATED ORGANELLES, PIGMENT GRANULES, MELANOCYTES, PROTEIN RAB38, MEMBRANE, EXPRESSION, GTPASES, BIOGENESIS, Developmental Biology, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: The Journal of Cell Biology
ISSN: 1540-8140
Language: eng
23 October 2006Published
PubMed ID: 17043139
Web of Science ID: WOS:000241575500009
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