2009
DOI: 10.1091/mbc.e08-07-0710
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Localization to Mature Melanosomes by Virtue of Cytoplasmic Dileucine Motifs Is Required for Human OCA2 Function

Abstract: Oculocutaneous albinism type 2 is caused by defects in the gene OCA2, encoding a pigment cell-specific, 12-transmembrane domain protein with homology to ion permeases. The function of the OCA2 protein remains unknown, and its subcellular localization is under debate. Here, we show that endogenous OCA2 in melanocytic cells rapidly exits the endoplasmic reticulum (ER) and thus does not behave as a resident ER protein. Consistently, exogenously expressed OCA2 localizes within melanocytes to melanosomes, and, like… Show more

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Cited by 67 publications
(95 citation statements)
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References 70 publications
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“…Both of these proteins are necessary for the processing and trafficking of tyrosinase and other proteins necessary for melanin synthesis in the melanosomes (31), and may also be important to maintain melanosomal pH (32). Similar to Slc15a4, the OCA2 polypeptide sequence contains dileucine motifs in its N-terminal region that are recognized by AP-3, which directs OCA2 to the mature melanosome (33).…”
Section: Discussionmentioning
confidence: 99%
“…Both of these proteins are necessary for the processing and trafficking of tyrosinase and other proteins necessary for melanin synthesis in the melanosomes (31), and may also be important to maintain melanosomal pH (32). Similar to Slc15a4, the OCA2 polypeptide sequence contains dileucine motifs in its N-terminal region that are recognized by AP-3, which directs OCA2 to the mature melanosome (33).…”
Section: Discussionmentioning
confidence: 99%
“…S5). This OCA2 loop was previously used to add other tags without affecting the protein trafficking and function (26). Providing OCA2 functions in chloride transport, we used the nonconductive V443I pore mutant to avoid any change MELOPS expression might cause on melanosomal pH (9).…”
Section: Tpc2 Regulates Melanosome Luminal Phmentioning
confidence: 99%
“…These integral membrane proteins are recognized as melanosome cargoes in part by conventional cytoplasmically-exposed endosomal sorting signals (7, 19, 165, 168, 181, 189), likely functioning in concert with lumenal determinants (63, 168). The sorting signals in TYR, TYRP1 and OCA2 conform to the acidic dileucine-based consensus sequence of [D/E]XXXL[L/I] (14).…”
Section: Protein Sorting To Mature Melanosomesmentioning
confidence: 99%