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Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion

Item Type:Article
Title:Barttin is a Cl- channel beta-subunit crucial for renal Cl- reabsorption and inner ear K+ secretion
Creators Name:Estevez, R. and Boettger, T. and Stein, V. and Birkenhaeger, R. and Otto, E. and Hildebrandt, F. and Jentsch, T.J.
Abstract:Renal salt loss in Bartter's syndrome is caused by impaired transepithelial transport in the loop of Henle. Sodium chloride is taken up apically by the combined activity of NKCC2 (Na+-K--2Cl- cotransporters) and ROMK potassium channels. Chloride ions exit from the cell through basolateral ClC-Kb chloride channels. Mutations in the three corresponding genes have been identified that correspond to Bartter's syndrome types 1-3. The gene encoding the integral membrane protein barttin is mutated in a form of Bartter's syndrome that is associated with congenital deafness and renal failure. Here we show that barttin acts as an essential beta-subunit for ClC-Ka and ClC-Kb chloride channels, with which it colocalizes in basolateral membranes of renal tubules and of potassium-secreting epithelia of the inner ear. Disease-causing mutations in either ClC-Kb or barttin compromise currents through heteromeric channels. Currents can be stimulated further by mutating a proline-tyrosine (PY) motif on barttin. This work describes the first known beta-subunit for CLC chloride channels and reveals that heteromers formed by ClC-K and barttin are crucial for renal salt reabsorption and potassium recycling in the inner ear.
Keywords:Absorption, Anion Transport Proteins, Bartter Syndrome, Cell Line, Chloride Channels, Chlorides, Inner Ear, Kidney, Kidney Tubules, Membrane Proteins, Potassium, Protein Subunits, Recombinant Proteins, Animals, Xenopus
Publisher:Nature Publishing Group
Page Range:558-561
Date:29 November 2001
Official Publication:https://doi.org/10.1038/35107099
PubMed:View item in PubMed

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