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Elife. 2014 Dec 16;3:e04543. doi: 10.7554/eLife.04543.

An intracellular anion channel critical for pigmentation.

Author information

1
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University, Providence, United States.
2
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, United States.

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.

KEYWORDS:

albinism; biophysics; cell biology; human; ion channel; melanosome; structural biology

PMID:
25513726
PMCID:
PMC4270065
DOI:
10.7554/eLife.04543
[Indexed for MEDLINE]
Free PMC Article

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