Leucine-rich repeat-containing protein 8E is a protein that in humans is encoded by the LRRC8Egene.[1] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8C, and LRRC8D, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel.[2] Volume-Regulated Anion Channels (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,[3] and that is not the only function these channels have been linked to.
While LRRC8E is one of many proteins that can be part of VRAC, research has found that it is not as crucial to the activity of the channel in comparison to LRRC8A and LRRC8D.[4][5][6] However, while we know that LRRC8A and LRRC8D are necessary for VRAC function, other studies have found that they are not sufficient for the full range of usual VRAC activity.[7] This is where the other LRRC8 proteins come in, such as LRRC8E, as the different composition of these subunits affects the range of specificity for VRACs.[8][6]
In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5.[9]
Specifically for LRRC8E, there has been a recent study that found that this gene was nominally associated with panic disorder.[10]
↑Voss FK, Ullrich F, Münch J, Lazarow K, Lutter D, Mah N, Andrade-Navarro MA, von Kries JP, Stauber T, Jentsch TJ (May 2014). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC". Science. 344 (6184): 634–8. doi:10.1126/science.1252826. PMID24790029.
↑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.
↑Gregersen NO, Buttenschøn HN, Hedemand A, Nielsen MN, Dahl HA, Kristensen AS, Johansen O, Woldbye DP, Erhardt A, Kruse TA, Wang AG, Børglum AD, Mors O (December 2016). "Association between genes on chromosome 19p13.2 and panic disorder". Psychiatric Genetics. 26 (6): 287–292. doi:10.1097/YPG.0000000000000147. PMID27610895.
Further reading
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC1347501. PMID16381901.
Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (February 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID10718198.
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.
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.
Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, Wakamatsu A, Kimura K, Sakamoto K, Hatano N, Kawai Y, Ishii S, Saito K, Kojima S, Sugiyama T, Ono T, Okano K, Yoshikawa Y, Aotsuka S, Sasaki N, Hattori A, Okumura K, Nagai K, Sugano S, Isogai T (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Research. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID16303743.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
