Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene.[5] Researchers have found out that this protein, along with the other LRRC8 proteins LRRC8A, LRRC8B, LRRC8D, and LRRC8E, is sometimes a subunit of the heteromer protein Volume-Regulated Anion Channel.[6] 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,[7] and that is not the only function these channels have been linked to.

LRRC8C
Identifiers
AliasesLRRC8C, AD158, FAD158, leucine-rich repeat containing 8 family member C, leucine rich repeat containing 8 family member C, leucine rich repeat containing 8 VRAC subunit C
External IDsOMIM: 612889; MGI: 2140839; HomoloGene: 12997; GeneCards: LRRC8C; OMA:LRRC8C - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_032270

NM_133897

RefSeq (protein)

NP_115646

NP_598658

Location (UCSC)Chr 1: 89.63 – 89.77 MbChr 5: 105.67 – 105.76 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

While LRRC8C 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 LRRC8C, 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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171488Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000054720Ensembl, 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 F, Ullrich F, Münch J (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.
  7. ^ Jentsch TJ (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]
  8. ^ Hyzinski-García MC, Rudkouskaya A, Mongin A (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.
  9. ^ Yamada T, Wondergem R, Morrison R (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.
  10. ^ a b Planells-Cases R, Lutter D, Guyader C (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.
  11. ^ 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.
  12. ^ Lutter D, Ullrich F, Lueck JC (2017-03-15). "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 (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

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