Biology:LRRC8C

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Leucine-rich repeat-containing protein 8C is a protein that in humans is encoded by the LRRC8C gene.[1] 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.[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 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.[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 LRRC8C, 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". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=56262. 
  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.". Science 344 (6184): 634–8. doi:10.1126/science.1252826. PMID 24790029. Bibcode2014Sci...344..634V. http://edoc.mdc-berlin.de/14008/1/14008oa.pdf. 
  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. https://exlibris.colgate.edu:2231/pubmed/?term=VRACs%20and%20other%20ion%20channels%20and%20transporters%20in%20the%20regulation%20of%20cell%20volume%20and%20beyond. 
  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. 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. PMID 27688432. 
  6. 6.0 6.1 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. 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. 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". 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. PMID 14660746. 

Further reading