LRRC8A, AGM5, LRRC8, SWELL1, leucine-rich repeat containing 8 family member A, leucine rich repeat containing 8 family member A, leucine rich repeat containing 8 VRAC subunit A, HsLRRC8A
Leucine-rich repeat-containing protein 8A is a protein that in humans is encoded by the LRRC8Agene.[5] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8B, LRRC8C, LRRC8D, and LRRC8E, is a subunit of the heteromer protein volume-regulated anion channel (VRAC).[6] VRACs are crucial to the regulation of cell size by transporting chloride ions and various organic osmolytes, such as taurine or glutamate, across the plasma membrane,[7] and that is not the only function these channels have been linked to.
While LRRC8A is one of many proteins that can be part of VRAC, it is the most important subunit for the channel’s ability to function.[8][9] However, while we know it is necessary for VRAC function, other studies have found that it is not sufficient for the full range of usual VRAC activity.[10] This is where the other LRRC8 proteins come in, as the different composition of these subunits affects the range of specificity for VRACs.[11][12]
The transmembrane portion of LRRC8 proteins are similar to those in Pannexins.[13] LRRC8A alone can form a hexameric VRAC, for which the cyro-EM structure has been determined in its mice and human versions.[14][15][16]
In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5.[17]
^Jentsch TJ (May 2016). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (5): 293–307. doi:10.1038/nrm.2016.29. PMID27033257. S2CID40565653.
^Abascal, F; Zardoya, R (July 2012). "LRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell-cell communication". BioEssays. 34 (7): 551–60. doi:10.1002/bies.201100173. hdl:10261/124027. PMID22532330. S2CID24648128.
Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, Ozono K, Hara J (April 2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Letters. 564 (1–2): 147–52. doi:10.1016/S0014-5793(04)00332-1. PMID15094057. S2CID29283213.
Smits G, Kajava AV (July 2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Molecular Immunology. 41 (5): 561–2. doi:10.1016/j.molimm.2004.04.001. PMID15183935.
