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Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC.

Science (New York, N.Y.) (2014-05-03)
Felizia K Voss, Florian Ullrich, Jonas Münch, Katina Lazarow, Darius Lutter, Nancy Mah, Miguel A Andrade-Navarro, Jens P von Kries, Tobias Stauber, Thomas J Jentsch
ABSTRACT

Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide small interfering RNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated VRAC currents. Cells with disruption of all five LRRC8 genes required LRRC8A cotransfection with other LRRC8 isoforms to reconstitute VRAC currents. The isoform combination determined VRAC inactivation kinetics. Taurine flux and regulatory volume decrease also depended on LRRC8 proteins. Our work shows that VRAC defines a class of anion channels, suggests that VRAC is identical to the volume-sensitive organic osmolyte/anion channel VSOAC, and explains the heterogeneity of native VRAC currents.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Taurine, ≥99%
Sigma-Aldrich
Taurine, suitable for cell culture, meets USP testing specifications
Supelco
Taurine, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Taurine, BioUltra, ≥99.5% (T)
SAFC
Taurine
Sigma-Aldrich
Taurine, ≥98%, FG
Sigma-Aldrich
Anti-LRRC8B antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution