FEATURES

FAMILY

DESCRIPTION

Also known as LRC8A_MOUSE, Lrrc8a, Lrrc8. 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 (PubMed:30135305, PubMed:29769723). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Mediates efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (By similarity). 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 (PubMed:32277911). In contrast, complexes containing LRRC8D inhibit transport of 2'-3'-cGAMP (By similarity). 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 (By similarity). Can form functional channels by itself (in vitro) (By similarity). Involved in B-cell development: required for the pro-B cell to pre-B cell transition (PubMed:14660746, PubMed:24752297). Also required for T-cell development (PubMed:24752297). Required for myoblast differentiation: VRAC activity promotes membrane hyperpolarization and regulates insulin-stimulated glucose metabolism and oxygen consumption (PubMed:31387946, PubMed:32930093). 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 (PubMed:29371604, PubMed:29773801). 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 (By similarity). Hexamer; forms a trimer of dimers (PubMed:29769723, PubMed:30775971). Heterohexamer; oligomerizes with other LRRC8 proteins (LRRC8B, LRRC8C, LRRC8D and/or LRRC8E) to form a heterohexamer (PubMed:24782309, PubMed:29769723). Can form homohexamers in vitro, but these have lower conductance than heterohexamers (PubMed:29769723). Detected in a channel complex that contains LRRC8A, LRRC8C and LRRC8E (By similarity). In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist (Probable). Interact with GRB2 (PubMed:32930093).

EXTERNAL LINKS

Lrrc8a

Mutations

Mutation(s) distribution

Mutations table