title: Regulation of melanosome number, shape and movement in the zebrafish retinal pigment epithelium by OA1 and PMEL.
abstract: Analysis of melanosome biogenesis in the retinal pigment epithelium (RPE) is challenging because it occurs predominantly in a short embryonic time window. Here, we show that the zebrafish provides an ideal model system for studying this process because in the RPE the timing of melanosome biogenesis facilitates molecular manipulation using morpholinos. Morpholino-mediated knockdown of OA1 (also known as GPR143), mutations in the human homologue of which cause the most common form of human ocular albinism, induces a major reduction in melanosome number, recapitulating a key feature of the mammalian disease where reduced melanosome numbers precede macromelanosome formation. We further show that PMEL, a key component of mammalian melanosome biogenesis, is required for the generation of cylindrical melanosomes in zebrafish, which in turn is required for melanosome movement into the apical processes and maintenance of photoreceptor integrity. Spherical and cylindrical melanosomes containing similar melanin volumes co-exist in the cell body but only cylindrical melanosomes enter the apical processes. Taken together, our findings indicate that melanosome number and shape are independently regulated and that melanosome shape controls a function in the RPE that depends on localisation in the apical processes.
authors.affiliation: UCL Institute of Ophthalmology, London EC1V 9EL, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Burgoyne
authors.affiliation: UCL Institute of Ophthalmology, London EC1V 9EL, UK MRC Laboratory for Molecular Cell Biology, University College, London WC1E 6BT, UK.
authors.forename: Marie N
authors.initials: MN
authors.lastname: O'Connor
authors.affiliation: NHLI, Imperial College, London SW7 2AZ, UK.
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
authors.affiliation: MRC Laboratory for Molecular Cell Biology, University College, London WC1E 6BT, UK.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Cutler
authors.affiliation: UCL Institute of Ophthalmology, London EC1V 9EL, UK c.futter@ucl.ac.uk.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Futter
mesh_terms: D016117:Albinism, Ocular / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D020460:Melanosomes / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000196:embryology / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000606741:GPR143 protein, zebrafish; C000606742:PMELa protein, zebrafish; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins
keywords: Melanosome; OA1; PMEL; Retinal pigment epithelium