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Vol. 15, Issue 5, 2264-2275, May 2004
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¶
* Division of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom;
Centre of Ophthalmology, Biomedical Institute for Research in Light and Image, University of Coimbra, 3000-354 Coimbra, Portugal;
Department of Pathophysiology of Vision and Neuro-ophthalmology, University Eye Hospital, Tübingen, Germany; and
Cell and Molecular Biology, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, London SW7 2AZ, United Kingdom
Submitted October 30, 2003;
Revised February 6, 2004;
Accepted February 6, 2004
Monitoring Editor: Juan S. Bonifacino
Melanosomes within the retinal pigment epithelium (RPE) of mammals have long been thought to exhibit no movement in response to light, unlike fish and amphibian RPE. Here we show that the distribution of melanosomes within the mouse RPE undergoes modest but significant changes with the light cycle. Two hours after light onset, there is a threefold increase in the number of melanosomes in the apical processes that surround adjacent photoreceptors. In skin melanocytes, melanosomes are motile and evenly distributed throughout the cell periphery. This distribution is due to the interaction with the cortical actin cytoskeleton mediated by a tripartite complex of Rab27a, melanophilin, and myosin Va. In ashen (Rab27a null) mice RPE, melanosomes are unable to move beyond the adherens junction axis and do not enter apical processes, suggesting that Rab27a regulates melanosome distribution in the RPE. Unlike skin melanocytes, the effects of Rab27a are mediated through myosin VIIa in the RPE, as evidenced by the similar melanosome distribution phenotype observed in shaker-1 mice, defective in myosin VIIa. Rab27a and myosin VIIa are likely to be required for association with and movement through the apical actin cytoskeleton, which is a prerequisite for entry into the apical processes.
¶ Corresponding author. E-mail address: m.seabra{at}imperial.ac.uk.
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