An intracellular anion channel critical for pigmentation

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Albinism, Oculocutaneous / metabolism
  • Animals
  • Anions / metabolism
  • Anura
  • Carrier Proteins / metabolism
  • Cell Line
  • Chloride Channels / metabolism*
  • Endosomes / metabolism
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Intracellular Space / metabolism*
  • Lysosomes / metabolism
  • Melanosomes / metabolism
  • Membrane Proteins / metabolism
  • Mice
  • Mutation / genetics
  • Pigmentation*

Substances

  • Anions
  • Carrier Proteins
  • Chloride Channels
  • Membrane Proteins
  • Green Fluorescent Proteins
  • P protein, mouse

Supplementary concepts

  • Oculocutaneous albinism type 2