Lynch, JW;
Sivilotti, LG;
Smart, TG;
(2021)
Glycine receptors in GtoPdb v.2021.3.
IUPHAR/BPS Guide to Pharmacology CITE
, 2021
(3)
pp. 1-7.
10.2218/gtopdb/f73/2021.3.
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Abstract
The inhibitory glycine receptor (nomenclature as agreed by the NC-IUPHAR Subcommittee on Glycine Receptors) is a member of the Cys-loop superfamily of transmitter-gated ion channels that includes the zinc activated channels, GABA_{A}, nicotinic acetylcholine and 5-HT_{3} receptors and Zn2^{+}_{-} activated channels. The receptor is expressed either as a homo-pentamer of α subunits, or a complex now thought to harbour 2α and 3β subunits [33, 7], that contain an intrinsic anion channel. Four differentially expressed isoforms of the α-subunit (α1-α4) and one variant of the β-subunit (β1, GLRB, P48167) have been identified by genomic and cDNA cloning. Further diversity originates from alternative splicing of the primary gene transcripts for α1 (α1^{INS} and α1^{del} ), α2 (α2A and α2B), α3 (α3S and α3L) and β (βΔ7) subunits and by mRNA editing of the α2 and α3 subunit [83, 93, 21]. Both α2 splicing and α3 mRNA editing can produce subunits (i.e., α2B and α3P185L) with enhanced agonist sensitivity. Predominantly, the adult form of the receptor contains α1 (or α3) and β subunits whereas the immature form is mostly composed of only α2 subunits. The &a;pha;4 subunit is a pseudogene in humans. High resolution molecular structures are available for the α1 and α3 homomeric receptors [50, 20]. As in other Cys-loop receptors, the orthosteric binding site for agonists and the competitive antagonist strychnine is formed at the interfaces between the subunits’ extracellular domains. Inclusion of the β-subunit in the pentameric glycine receptor contributes to agonist binding, reduces single channel conductance and alters pharmacology. The β-subunit also anchors the receptor, via an amphipathic sequence within the large intracellular loop region, to gephyrin. This a cytoskeletal attachment protein that binds to a number of subsynaptic proteins involved in cytoskeletal structure and thus clusters and anchors hetero-oligomeric receptors to the synapse [56, 54, 88]. G protein βγ subunits enhance the open state probability of native and recombinant glycine receptors by association with domains within the large intracellular loop [124, 123]. Intracellular chloride concentration modulates the kinetics of native and recombinant glycine receptors [96]. Intracellular Ca^{2+} appears to increase native and recombinant glycine receptor affinity, prolonging channel open events, by a mechanism that does not involve phosphorylation [27]. Extracellular Zn^{2+} potentiates GlyR function at nanomolar concentrations [86]. and causes inhibition at higher micromolar concentrations (17).
Type: | Article |
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Title: | Glycine receptors in GtoPdb v.2021.3 |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.2218/gtopdb/f73/2021.3 |
Publisher version: | https://doi.org/10.2218/gtopdb/F73/2021.3 |
Language: | English |
Additional information: | © 2021 IUPHAR/BPS Guide to Pharmacology CITE. This Open Access journal is hosted by the University of Edinburgh Journal Hosting Service. All material is licensed under a Creative Commons Attribution-ShareAlike 4.0 International (CC BY-SA 4.0) licence (https://creativecommons.org/licenses/by-sa/4.0/). |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
URI: | https://discovery.ucl.ac.uk/id/eprint/10136316 |
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