title: An intracellular anion channel critical for pigmentation.
abstract: Intracellular ion channels are essential regulators of organellar and cellular function, yet the molecular identity and physiological role of many of these channels remains elusive. In particular, no ion channel has been characterized in melanosomes, organelles that produce and store the major mammalian pigment melanin. Defects in melanosome function cause albinism, characterized by vision and pigmentation deficits, impaired retinal development, and increased susceptibility to skin and eye cancers. The most common form of albinism is caused by mutations in oculocutaneous albinism II (OCA2), a melanosome-specific transmembrane protein with unknown function. Here we used direct patch-clamp of skin and eye melanosomes to identify a novel chloride-selective anion conductance mediated by OCA2 and required for melanin production. Expression of OCA2 increases organelle pH, suggesting that the chloride channel might regulate melanin synthesis by modulating melanosome pH. Thus, a melanosomal anion channel that requires OCA2 is essential for skin and eye pigmentation.
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Bellono
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Iliana E
authors.initials: IE
authors.lastname: Escobar
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States.
authors.forename: Ariel J
authors.initials: AJ
authors.lastname: Lefkovith
authors.affiliation: Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marks
authors.affiliation: Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
authors.forename: Elena
authors.initials: E
authors.lastname: Oancea
mesh_terms: D016115:Albinism, Oculocutaneous / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism; D001001:Anura; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D018118:Chloride Channels / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D010858:Pigmentation
chemical_list: D000838:Anions; D002352:Carrier Proteins; D018118:Chloride Channels; D008565:Membrane Proteins; D049452:Green Fluorescent Proteins; C076239:P protein, mouse
keywords: albinism; biophysics; cell biology; human; ion channel; melanosome; structural biology