QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 15, Issue 5, 2264-2275, May 2004

This Article Full Text Full Text (PDF) All Versions of this Article: E03-10-0772v1 15/5/2264    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Futter, C. E. Articles by Seabra, M. C. Search for Related Content PubMed PubMed Citation Articles by Futter, C. E. Articles by Seabra, M. C.

The Role of Rab27a in the Regulation of Melanosome Distribution within Retinal Pigment Epithelial Cells

Clare E. Futter ^*, José S. Ramalho , Gesine B. Jaissle , Mathias W. Seeliger , and Miguel C. Seabra  ^¶

^* 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.

This article has been cited by other articles:

				V. S. Lopes, C. Wasmeier, M. C. Seabra, and C. E. Futter Melanosome Maturation Defect in Rab38-deficient Retinal Pigment Epithelium Results in Instability of Immature Melanosomes during Transient Melanogenesis Mol. Biol. Cell, October 1, 2007; 18(10): 3914 - 3927. [Abstract] [Full Text] [PDF]

				P. D. Fairbank, C. Lee, A. Ellis, J. D. Hildebrand, J. M. Gross, and J. B. Wallingford Shroom2 (APXL) regulates melanosome biogenesis and localization in the retinal pigment epithelium Development, October 15, 2006; 133(20): 4109 - 4118. [Abstract] [Full Text] [PDF]

				M. L. Dietz, T. M. Bernaciak, F. Vendetti, J. M. Kielec, and J. D. Hildebrand Differential Actin-dependent Localization Modulates the Evolutionarily Conserved Activity of Shroom Family Proteins J. Biol. Chem., July 21, 2006; 281(29): 20542 - 20554. [Abstract] [Full Text] [PDF]

				E. F. Nandrot, M. Anand, M. Sircar, and S. C. Finnemann Novel role for {alpha}vbeta5-integrin in retinal adhesion and its diurnal peak Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1256 - C1262. [Abstract] [Full Text] [PDF]

				T. S. Kuroda and M. Fukuda Functional Analysis of Slac2-c/MyRIP as a Linker Protein between Melanosomes and Myosin VIIa J. Biol. Chem., July 29, 2005; 280(30): 28015 - 28022. [Abstract] [Full Text] [PDF]

				M. Fukuda Versatile Role of Rab27 in Membrane Trafficking: Focus on the Rab27 Effector Families J. Biochem., January 1, 2005; 137(1): 9 - 16. [Abstract] [Full Text] [PDF]

				D. Gibbs, S. M. Azarian, C. Lillo, J. Kitamoto, A. E. Klomp, K. P. Steel, R. T. Libby, and D. S. Williams Role of myosin VIIa and Rab27a in the motility and localization of RPE melanosomes J. Cell Sci., December 15, 2004; 117(26): 6473 - 6483. [Abstract] [Full Text] [PDF]