LRRC8 N termini influence pore properties and gating of volume-regulated anion channels (VRACs).

ABSTRACT: Volume-regulated anion channels (VRACs) are crucial for cell volume regulation and have various roles in physiology and pathology. VRACs were recently discovered to be formed by heteromers of leucine-rich repeat-containing 8 (LRRC8) proteins. However, the structural determinants of VRAC permeation and gating remain largely unknown. We show here that the short stretch preceding the first LRRC8 transmembrane domain determines VRAC conductance, ion permeability, and inactivation gating. Substituted-cysteine accessibility studies revealed that several of the first 15 LRRC8 residues are functionally important and exposed to a hydrophilic environment. Substituting glutamate 6 with cysteine decreased the amplitudes of swelling-activated I_Cl,vol currents, strongly increased iodid

SUBMITTER: Zhou P 

PROVIDER: S-EPMC6120214 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature