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 .
Cell membrane ; Multi-pass membrane protein . Lysosome membrane ; Multi-pass membrane protein . Mainly localizes to the cell membrane, with some intracellular localization to lysosomes. .
Expressed in brain, kidney, ovary, lung, liver, heart, and fetal brain and liver. Found at high levels in bone marrow; lower levels are detected in peripheral blood cells. Expressed on T-cells as well as on B-lineage cells.
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