Protein Details: Volume-regulated anion channel subunit LRRC8A

Function

Essential component of the volume-regulated anion channel (VRAC; also named VSOAC channel); an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes . The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine . Mediates efflux of amino acids; such as aspartate and glutamate; in response to osmotic stress . LRRC8A and LRRC8D are required for the uptake of the drug cisplatin . In complex with LRRC8C or LRRC8E; acts as a transporter of immunoreactive cyclic dinucleotide GMP-AMP (2-3-cGAMP); an immune messenger produced in response to DNA virus in the cytosol: mediates both import and export of 2-3-cGAMP; thereby promoting transfer of 2-3-cGAMP to bystander cells . In contrast; complexes containing LRRC8D inhibit transport of 2-3-cGAMP . Required for in vivo channel activity; together with at least one other family member (LRRC8B; LRRC8C; LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition . Can form functional channels by itself (in vitro) . Involved in B-cell development: required for the pro-B cell to pre-B cell transition . Also required for T-cell development (By similarity). Required for myoblast differentiation: VRAC activity promotes membrane hyperpolarization and regulates insulin-stimulated glucose metabolism and oxygen consumption (By similarity). Also acts as a regulator of glucose-sensing in pancreatic beta cells: VRAC currents; generated in response to hypotonicity- or glucose-induced beta cell swelling; depolarize cells; thereby causing electrical excitation; leading to increase glucose sensitivity and insulin secretion . Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles; which store and then expel excess water to maintain cytosolic water homeostasis .

Sequence

PDB Structures

Ligand Binding