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Rab27a regulates the peripheral distribution of melanosomes in melanocytes.

Abstract
Rab GTPases are regulators of intracellular membrane traffic. We report a possible function of Rab27a, a protein implicated in several diseases, including Griscelli syndrome, choroideremia, and the Hermansky-Pudlak syndrome mouse model, gunmetal. We studied endogenous Rab27a and overexpressed enhanced GFP-Rab27a fusion protein in several cultured melanocyte and melanoma-derived cell lines. In pigmented cells, we observed that Rab27a decorates melanosomes, whereas in nonpigmented cells Rab27a colocalizes with melanosome-resident proteins. When dominant interfering Rab27a mutants were expressed in pigmented cells, we observed a redistribution of pigment granules with perinuclear clustering. This phenotype is similar to that observed by others in melanocytes derived from the ashen and dilute mutant mice, which bear mutations in the Rab27a and MyoVa loci, respectively. We also found that myosinVa coimmunoprecipitates with Rab27a in extracts from melanocytes and that both Rab27a and myosinVa colocalize on the cytoplasmic face of peripheral melanosomes in wild-type melanocytes. However, the amount of myosinVa in melanosomes from Rab27a-deficient ashen melanocytes is greatly reduced. These results, together with recent data implicating myosinVa in the peripheral capture of melanosomes, suggest that Rab27a is necessary for the recruitment of myosinVa, so allowing the peripheral retention of melanosomes in melanocytes.
AuthorsA N Hume, L M Collinson, A Rapak, A Q Gomes, C R Hopkins, M C Seabra
JournalThe Journal of cell biology (J Cell Biol) Vol. 152 Issue 4 Pg. 795-808 (Feb 19 2001) ISSN: 0021-9525 [Print] United States
PMID11266470 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Intermediate Filament Proteins
  • Myo5a protein, mouse
  • rab27 GTP-Binding Proteins
  • Myosin Type V
  • Rab27a protein, mouse
  • Myosin Heavy Chains
  • rab GTP-Binding Proteins
Topics
  • Animals
  • Cell Compartmentation
  • Choroideremia
  • Hermanski-Pudlak Syndrome
  • Intermediate Filament Proteins (metabolism)
  • Melanocytes (metabolism, ultrastructure)
  • Melanoma, Experimental
  • Melanosomes (chemistry, metabolism)
  • Mice
  • Mutation
  • Myosin Heavy Chains
  • Myosin Type V
  • Protein Binding
  • Tumor Cells, Cultured
  • rab GTP-Binding Proteins (genetics, isolation & purification, metabolism)
  • rab27 GTP-Binding Proteins

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