Discovery of CLC transport proteins: cloning, structure, function and pathophysiology.

Abstract

After providing a personal description of the convoluted path leading 25 years ago to the molecular identification of the Torpedo Cl(-) channel ClC-0 and the discovery of the CLC gene family, I succinctly describe the general structural and functional features of these ion transporters before giving a short overview of mammalian CLCs. These can be categorized into plasma membrane Cl(-) channels and vesicular Cl(-) /H(+) -exchangers. They are involved in the regulation of membrane excitability, transepithelial transport, extracellular ion homeostasis, endocytosis and lysosomal function. Diseases caused by CLC dysfunction include myotonia, neurodegeneration, deafness, blindness, leukodystrophy, male infertility, renal salt loss, kidney stones and osteopetrosis, revealing a surprisingly broad spectrum of biological roles for chloride transport that was unsuspected when I set out to clone the first voltage-gated chloride channel.

• Authors: Thomas J Jentsch
• Journal: The Journal of physiology (J Physiol) Vol. 593 Issue 18 Pg. 4091-109 (Sep 15 2015) ISSN: 1469-7793 [Electronic] England
• PMID: 25590607 (Publication Type: Journal Article, Review)
• Copyright: © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Chemical References

• Carrier Proteins
• Chloride Channels
• Chlorides

Topics

• Animals
• Biological Transport (physiology)
• Carrier Proteins (metabolism)
• Cell Membrane (metabolism)
• Chloride Channels (metabolism)
• Chlorides (metabolism)
• Cloning, Molecular
• Humans
• Ion Transport (physiology)