LRRC8B

LRRC8B
Identifiers
Aliases	LRRC8B , TA-LRRP, TALRRP, leucine-rich repeat containing 8 family member B, leucine rich repeat containing 8 family member B, leucine rich repeat containing 8 VRAC subunit B
External IDs	OMIM: 612888; MGI: 2141353; GeneCards: LRRC8B
Gene location (Human) Chr. Chromosome 1 (human) [1] Band 1p22.2 Start 89,524,829 bp [1] End 89,597,861 bp [1]
Gene location (Mouse) Chr. Chromosome 5 (mouse) [2] Band 5|5 E5 Start 105,563,641 bp [2] End 105,637,940 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle temporal gyrus endothelial cell oocyte secondary oocyte orbitofrontal cortex superior frontal gyrus Brodmann area 46 primary visual cortex postcentral gyrus Top expressed in secondary oocyte otolith organ utricle vestibular membrane of cochlear duct trigeminal ganglion zygote Region I of hippocampus proper primary oocyte spermatid primary motor cortex More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding volume-sensitive anion channel activity Cellular component cytoplasm integral component of membrane membrane endoplasmic reticulum endoplasmic reticulum membrane plasma membrane ion channel complex integral component of plasma membrane Biological process ion transport signal transduction transmembrane transport inorganic anion transport cell volume homeostasis anion transmembrane transport Sources:Amigo / QuickGO
Orthologs Databases NCBI: entry; OMA: entry Species Human Mouse Entrez 23507 433926 Ensembl ENSG00000197147 ENSMUSG00000070639 UniProt Q6P9F7 Q5DU41 RefSeq (mRNA) NM_001134476 NM_015350 NM_001369817 NM_001369819 NM_001033550 RefSeq (protein) NP_001127948 NP_056165 NP_001356746 NP_001356748 NP_001028722 Location (UCSC) Chr 1: 89.52 – 89.6 Mb Chr 5: 105.56 – 105.64 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Leucine-rich repeat-containing protein 8B is a protein that in humans is encoded by the LRRC8B gene. ^[5] 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). ^[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 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. ^{[8] [9] [10]} 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. ^[11] 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. ^{[12] [10]}

In addition to its role in VRACs, the LRRC8 protein family is also associated with agammaglobulinemia-5. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000197147 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000070639 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: LRRC8A leucine rich repeat containing 8 family, member A".
6. Voss FK, Ullrich F, Münch J, Lazarow K, Lutter D, Mah N, et al. (May 2014). "Identification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC". Science (Submitted manuscript). 344 (6184). New York, N.Y.: 634–638. Bibcode:2014Sci...344..634V. doi:10.1126/science.1252826. PMID   24790029. S2CID   24709412.
7. 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. PMID   27033257. S2CID   40565653.^{[ permanent dead link ]}
8. Hyzinski-García MC, Rudkouskaya A, Mongin AA (November 2014). "LRRC8A protein is indispensable for swelling-activated and ATP-induced release of excitatory amino acids in rat astrocytes". The Journal of Physiology. 592 (22): 4855–4862. doi:10.1113/jphysiol.2014.278887. PMC   4259531 . PMID   25172945.
9. Yamada T, Wondergem R, Morrison R, Yin VP, Strange K (October 2016). "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.
10. Planells-Cases R, Lutter D, Guyader C, Gerhards NM, Ullrich F, Elger DA, et al. (December 2015). "Subunit composition of VRAC channels determines substrate specificity and cellular resistance to Pt-based anti-cancer drugs". The EMBO Journal. 34 (24): 2993–3008. doi:10.15252/embj.201592409. PMC   4687416 . PMID   26530471.
11. Okada T, Islam MR, Tsiferova NA, Okada Y, Sabirov RZ (March 2017). "Specific and essential but not sufficient roles of LRRC8A in the activity of volume-sensitive outwardly rectifying anion channel (VSOR)". Channels. 11 (2). Austin, Tex.: 109–120. doi:10.1080/19336950.2016.1247133. PMC   5398601 . PMID   27764579.
12. Lutter D, Ullrich F, Lueck JC, Kempa S, Jentsch TJ (March 2017). "Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels". Journal of Cell Science. 130 (6): 1122–1133. doi: 10.1242/jcs.196253 . PMID   28193731.
13. Sawada A, Takihara Y, Kim JY, Matsuda-Hashii Y, Tokimasa S, Fujisaki H, et al. (December 2003). "A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans". The Journal of Clinical Investigation. 112 (11): 1707–1713. doi:10.1172/JCI18937. PMC   281644 . PMID   14660746.

Further reading

• Eggermont J, Trouet D, Carton I, Nilius B (2001). "Cellular function and control of volume-regulated anion channels". Cell Biochemistry and Biophysics . 35 (3): 263–274. doi:10.1385/CBB:35:3:263. PMID   11894846. S2CID   31821726.
• Mongin A (2016). "Volume-regulated anion channel – a frenemy within the brain". Pflugers Archiv. 468 (3): 421–441. doi:10.1007/s00424-015-1765-6. PMC   4752865 . PMID   26620797.
• 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 . PMID   10718198.
• Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, et al. (October 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research. 13 (10): 2265–2270. doi:10.1101/gr.1293003. PMC   403697 . PMID   12975309.
• Kubota K, Kim JY, Sawada A, Tokimasa S, Fujisaki H, Matsuda-Hashii Y, et al. (April 2004). "LRRC8 involved in B cell development belongs to a novel family of leucine-rich repeat proteins". FEBS Letters. 564 (1–2): 147–152. Bibcode:2004FEBSL.564..147K. doi: 10.1016/S0014-5793(04)00332-1 . PMID   15094057.
• Smits G, Kajava AV (2004). "LRRC8 extracellular domain is composed of 17 leucine-rich repeats". Molecular Immunology. 41 (5): 561–562. doi:10.1016/j.molimm.2004.04.001. PMID   15183935.
• Otsuki T, Ota T, Nishikawa T, Hayashi K, Suzuki Y, Yamamoto J, et al. (2005). "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): 117–126. doi: 10.1093/dnares/12.2.117 . PMID   16303743.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi: 10.1016/j.cell.2006.09.026 . PMID   17081983.