I am a
Home I AM A Search Login

Papers of the Week

Papers: 1 Oct 2022 - 7 Oct 2022

2022 Oct 05

Cell Mol Life Sci



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


Lemmens V, Thevelein B, Vella Y, Kankowski S, Leonhard J, Mizuno H, Rocha S, Brône B, Meier JC, Hendrix J
Cell Mol Life Sci. 2022 Oct 05; 79(11):540.
PMID: 36197517.


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.