Assembly and cell surface expression of heteromeric and homomeric γ-aminobutyric acid type A receptors

Abstract

The ability of differing subunit combinations of γ-aminobutyric acid type A (GABAA) receptors produced from murine α1-, α2, and γ2L subunits to form functional cell surface receptors was analyzed in both A293 cells and Xenopus oocytes using a combination of molecular, electrophysiological, biochemical, and morphological approaches. The results revealed that GABAA receptor assembly occurred within the endoplasmic reticulum and involved the interaction with the chaperone molecules immunoglobulin heavy chain binding protein and calnexin. Despite all three subunits possessing the ability to oligomerize with each other, only α1β2 and α1β2γ2L subunit combinations could produce functional surface expression in a process that was not dependent on N-linked glycosylation. Single subunits and the α1γ2L and β2γ2L combinations were retained within the endoplasmic reticulum. These results suggest that receptor assembly occurs by defined pathways, which may serve to limit the diversity of GABAA receptors that exist on the surface of neurons.