Burgoyne, T; Jolly, R; Martin-Martin, B; Seabra, MC; Piccirillo, R; Schiaffino, MV; Futter, CE; (2013) Expression of OA1 limits the fusion of a subset of MVBs with lysosomes; a mechanism likely involved in the initial biogenesis of melanosomes. Journal of Cell Science , 126 (22) 10.1242/jcs.128561.

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Abstract

Multivesicular endosomes/bodies (MVBs) deliver proteins like activated EGF receptors (EGFR) to the lysosome for degradation, and, in pigmented cells, MVBs containing PMEL are an initial stage in melanosome biogenesis. The mechanisms regulating numbers and fate of different populations of MVB are unclear. Here we focus on the role of the G protein coupled receptor, OA1, which is expressed exclusively in pigmented cells and mutations in which cause the most common type of ocular albinism. By exogenously expressing PMEL HeLa cells have been shown to form MVBs resembling early stage melanosomes. To focus on the role of OA1 in the initial stages of melanosome biogenesis we take advantage of the absence of the later stages of melanosome maturation in HeLa cells to determine whether OA1 activity can regulate MVB number and fate. Expression of wild type but not OA1 mutants carrying inactivating mutations/deletions causes MVB numbers to increase. Whilst OA1 expression has no effect on delivery of EGFR-containing MVBs to the lysosome it inhibits the lysosomal delivery of PMEL and PMEL-containing MVBs accumulate. We propose that OA1 activity delays delivery of PMEL-containing MVBs to the lysosome to allow time for melanin synthesis and commitment to melanosome biogenesis.

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