Molecular determinants of glycine receptor subunit assembly

The inhibitory glycine receptor (GlyR) is a pentameric transmembrane protein composed of homologous α and β subunits. Single expression of α subunits generates functional homo‐oligomeric GlyRs, whereas the β subunit requires a co‐expressed α subunit to assemble into hetero‐oligomeric channels of invariant stoichiometry (α 3 β 2 ). Here, we identified eight amino acid residues within the N‐terminal region of the α1 subunit that are required for the formation of homo‐oligomeric GlyR channels. We show that oligomerization and N‐glycosylationq of the α1 subunit are required for transit from the endoplasmic reticulum to the Golgi apparatus and later compartments, and that addition of simple carbohydrate side chains occurs prior to GlyR subunit assembly. Our data are consistent with both intersubunit surface and conformational differences determining the different assembly behaviour of GlyR α and β subunits.