ASSEMBLY AND CELL-SURFACE EXPRESSION OF HETEROMERIC AND HOMOMERIC GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTORS

The ability of differing subunit combinations of gamma-aminobutyric ac id type A (GABA(A)) receptors produced from murine alpha 1, beta 2, an d gamma 2L subunits to form functional cell surface receptors was anal yzed in both A293 cells and Xenopus oocytes using a combination of mol ecular, electrophysiological, biochemical, and morphological approache s. The results revealed that GABA(A) receptor assembly occurred within the endoplasmic reticulum and involved the interaction with the chape rone molecules immunoglobulin heavy chain binding protein and calnexin . Despite all three subunits possessing the ability to oligomerize wit h each other, only alpha 1 beta 2 and alpha 1 beta 2 gamma 2L subunit combinations could produce functional surface expression in a process that was not dependent on N-linked glycosylation. Single subunits and the alpha 1 gamma 2L and beta 2 gamma 2L combinations were retained wi thin the endoplasmic reticulum. These results suggest that receptor as sembly occurs by defined pathways, which may serve to limit the divers ity of GABA(A) receptors that exist on the surface of neurons.