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Rab27a: A Key to Melanosome Transport in Human Melanocytes

Correspondence to: Philippe Bahadoran, Unité de Recherches sur la Biologie et la Physiopathologie de la Peau, INSERM U385, Faculté de Médecine, Avenue de Valombrose, 06107 Nice Cedex 2, France. Tel:33-4-93-37-77-90 Fax:33-4-93-81-14-04 E-mail:bahadora{at}unice.fr.

Normal pigmentation depends on the uniform distribution of melanin-containing vesicles, the melanosomes, in the epidermis. Griscelli syndrome (GS) is a rare autosomal recessive disease, characterized by an immune deficiency and a partial albinism that has been ascribed to an abnormal melanosome distribution. GS maps to 15q21 and was first associated with mutations in the myosin-V gene. However, it was demonstrated recently that GS can also be caused by a mutation in the Rab27a gene. These observations prompted us to investigate the role of Rab27a in melanosome transport. Using immunofluorescence and immunoelectron microscopy studies, we show that in normal melanocytes Rab27a colocalizes with melanosomes. In melanocytes isolated from a patient with GS, we show an abnormal melanosome distribution and a lack of Rab27a expression. Finally, reexpression of Rab27a in GS melanocytes restored melanosome transport to dendrite tips, leading to a phenotypic reversion of the diseased cells. These results identify Rab27a as a key component of vesicle transport machinery in melanocytes.

Key Words: melanocytes, melanosomes, transport, Rab27a, Griscelli syndrome

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