Structural highlights
Function
LRC8D_MOUSE Non-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:29773801, PubMed:36522427). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (By similarity). Plays a redundant role in the efflux of amino acids, such as aspartate, in response to osmotic stress family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (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 (PubMed:29773801). VRAC channels containing LRRC8D inhibit transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:36522427).[UniProtKB:Q7L1W4][1] [2]
References
- ↑ Stuhlmann T, Planells-Cases R, Jentsch TJ. LRRC8/VRAC anion channels enhance beta-cell glucose sensing and insulin secretion. Nat Commun. 2018 May 17;9(1):1974. doi: 10.1038/s41467-018-04353-y. PMID:29773801 doi:https://dx.doi.org/10.1038/s41467-018-04353-y
- ↑ Rutz S, Deneka D, Dittmann A, Sawicka M, Dutzler R. Structure of a volume-regulated heteromeric LRRC8A/C channel. Nat Struct Mol Biol. 2023 Jan;30(1):52-61. PMID:36522427 doi:10.1038/s41594-022-00899-0