9f16

Structural highlights

Function

LRC8C_HUMAN 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:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658, PubMed:28193731). Plays a redundant role in the efflux of amino acids, such as aspartate and glutamate, in response to osmotic stress (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:33171122). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731).^{[1] [2] [3] [4]}

References

1. ↑ Voss FK, Ullrich F, Munch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ. Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC. Science. 2014 May 9;344(6184):634-8. doi: 10.1126/science.1252826. Epub 2014 Apr , 10. PMID:24790029 doi:http://dx.doi.org/10.1126/science.1252826
2. ↑ Syeda R, Qiu Z, Dubin AE, Murthy SE, Florendo MN, Mason DE, Mathur J, Cahalan SM, Peters EC, Montal M, Patapoutian A. LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength. Cell. 2016 Jan 28;164(3):499-511. doi: 10.1016/j.cell.2015.12.031. PMID:26824658 doi:http://dx.doi.org/10.1016/j.cell.2015.12.031
3. ↑ Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ. Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels. J Cell Sci. 2017 Mar 15;130(6):1122-1133. doi: 10.1242/jcs.196253. Epub 2017 Feb , 13. PMID:28193731 doi:http://dx.doi.org/10.1242/jcs.196253
4. ↑ Lahey LJ, Mardjuki RE, Wen X, Hess GT, Ritchie C, Carozza JA, Böhnert V, Maduke M, Bassik MC, Li L. LRRC8A:C/E Heteromeric Channels Are Ubiquitous Transporters of cGAMP. Mol Cell. 2020 Nov 19;80(4):578-591.e5. PMID:33171122 doi:10.1016/j.molcel.2020.10.021