LRRC8B

Leucine-rich repeat-containing protein 8B is a protein that in humans is encoded by the LRRC8B gene. ^[1] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8C, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein volume-regulated anion channel (VRAC). ^[2] 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 LRRC8B 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 LRRC8B, 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]

References

1. "Entrez Gene: LRRC8A leucine rich repeat containing 8 family, member A".
2. Voss, Felizia; Ullrich, Florian; Münch, Jonas (2014-05-09). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC" (PDF). Science (Submitted manuscript). 344 (6184): 634–8. Bibcode:2014Sci...344..634V. doi:10.1126/science.1252826. PMID   24790029. S2CID   24709412.
3. Jentsch, Thomas J. (2016-05-17). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond" . Nature Reviews Molecular Cell Biology. 17 (2): 293–3017. doi:10.1038/nrm.2016.29. ISSN   1471-0072. PMID   27033257. S2CID   40565653.^{[ permanent dead link ]}
4. Hyzinski-García, María C; Rudkouskaya, Alena; Mongin, Alexander (2014-11-15). "LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes". The Journal of Physiology. 592 (22): 4855–62. doi:10.1113/jphysiol.2014.278887. PMC   4259531 . PMID   25172945.
5. Yamada, Toshiki; Wondergem, Robert; Morrison, Rebecca (2016-10-04). "Leucine-rich repeat containing protein LRRC8A is essential for swelling-activated Cl- currents and embryonic development in zebrafish". Physiological Reports. 4 (19): e12940. doi:10.14814/phy2.12940. PMC   5064130 . PMID   27688432.
6. Planells-Cases, Rosa; Lutter, Darius; Guyader, Charlotte (2015-12-14). "Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs". EMBO Journal. 34 (24): 2993–3008. doi:10.15252/embj.201592409. PMC   4687416 . PMID   26530471.
7. Okada, T; Islam, MR; Tsiferova, NA (2016-10-20). "Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)". Channels. 11 (2): 109–120. doi:10.1080/19336950.2016.1247133. PMC   5398601 . PMID   27764579.
8. Lutter, D; Ullrich, F; Lueck, JC (2017-03-15). "Selective transport of neurotransmitters and –modulators by distinct volume-regulated LRRC8 anion channels" (PDF). Journal of Cell Science. 130 (6): 1122–1133. doi: 10.1242/jcs.196253 . PMID   28193731.
9. Sawada, A; Takihara, Y; Kim, JY (December 2003). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". Journal of Clinical Investigation. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC   281644 . PMID   14660746.

Further reading

• Jentsch Thomas J (2016). "VRACs and other ion channels and transporters in the regulation of cell volume and beyond". Nature Reviews Molecular Cell Biology. 17 (2): 293–307. doi:10.1038/nrm.2016.29. PMID   27033257. S2CID   40565653.
• Eggermont D, Trouet I, Carton I, et al. (2001). "Cellular function and control of volume-regulated anion channels". Cell Biochemistry and Biophysics . 35 (3): 263–74. doi:10.1385/CBB:35:3:263. PMID   11894846. S2CID   31821726.
• Mongin A (2016). "Volume-regulated anion channel – a frenemy within the brain". Pflügers Archiv. 468 (3): 421–441. doi:10.1007/s00424-015-1765-6. PMC   4752865 . PMID   26620797.
• Nagase T, Kikuno R, Ishikawa KI, et al. (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 Res. 7 (1): 65–73. doi: 10.1093/dnares/7.1.65 . PMID   10718198.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC   403697 . PMID   12975309.
• Sawada A, Takihara Y, Kim JY, et al. (2004). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". J. Clin. Invest. 112 (11): 1707–13. doi:10.1172/JCI18937. PMC   281644 . PMID   14660746.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Kubota K, Kim JY, Sawada A, et al. (2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Lett. 564 (1–2): 147–52. Bibcode:2004FEBSL.564..147K. doi: 10.1016/S0014-5793(04)00332-1 . PMID   15094057.
• Humphray SJ, Oliver K, Hunt AR, et al. (2004). "DNA sequence and analysis of human chromosome 9". Nature. 429 (6990): 369–74. Bibcode:2004Natur.429..369H. doi:10.1038/nature02465. PMC   2734081 . PMID   15164053.
• Smits G, Kajava AV (2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Mol. Immunol. 41 (5): 561–2. doi:10.1016/j.molimm.2004.04.001. PMID   15183935.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Otsuki T, Ota T, Nishikawa T, et al. (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 Res. 12 (2): 117–26. doi: 10.1093/dnares/12.2.117 . PMID   16303743.
• Olsen JV, Blagoev B, Gnad F, et al. (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 . PMID   17081983.