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Hetero-pentamerization determines mobility and conductance of Glycine receptor α3 splice variants. | LitMetric

Hetero-pentamerization determines mobility and conductance of Glycine receptor α3 splice variants.

Cell Mol Life Sci

Dynamic Bioimaging Lab, Advanced Optical Microscopy Centre and Biomedical Research Institute, Hasselt University, Agoralaan C (BIOMED), 3590, Diepenbeek, Belgium.

Published: October 2022

AI Article Synopsis

Article Abstract

Glycine receptors (GlyRs) are ligand-gated pentameric chloride channels in the central nervous system. GlyR-α3 is a possible target for chronic pain treatment and temporal lobe epilepsy. Alternative splicing into K or L variants determines the subcellular fate and function of GlyR-α3, yet it remains to be shown whether its different splice variants can functionally co-assemble, and what the properties of such heteropentamers would be. Here, we subjected GlyR-α3 to a combined fluorescence microscopy and electrophysiology analysis. We employ masked Pearson's and dual-color spatiotemporal correlation analysis to prove that GlyR-α3 splice variants heteropentamerize, adopting the mobility of the K variant. Fluorescence-based single-subunit counting experiments revealed a variable and concentration ratio dependent hetero-stoichiometry. Via cell-attached single-channel electrophysiology we show that heteropentamers exhibit currents in between those of K and L variants. Our data are compatible with a model where α3 heteropentamerization fine-tunes mobility and activity of GlyR-α3 channels, which is important to understand and tackle α3 related diseases.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9534812PMC
http://dx.doi.org/10.1007/s00018-022-04506-9DOI Listing

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