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

Christopher N. Connolly, Belinda J. Krishek, Bernard J. McDonald, Trevor G. Smart, Stephen J. Moss

    Research output: Contribution to journalArticle

    269 Citations (Scopus)

    Abstract

    The ability of differing subunit combinations of gamma-aminobutyric acid type A (GABA(A)) receptors produced from murine alpha 1, beta 2, and gamma 2L 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 GABA(A) 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 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 within the endoplasmic reticulum. These results suggest that receptor assembly occurs by defined pathways, which may serve to limit the diversity of GABA(A) receptors that exist on the surface of neurons.

    Original languageEnglish
    Pages (from-to)89-96
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume271
    Issue number1
    DOIs
    Publication statusPublished - 5 Jan 1996

    Cite this

    Connolly, Christopher N. ; Krishek, Belinda J. ; McDonald, Bernard J. ; Smart, Trevor G. ; Moss, Stephen J. / Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 1. pp. 89-96.
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    abstract = "The ability of differing subunit combinations of gamma-aminobutyric acid type A (GABA(A)) receptors produced from murine alpha 1, beta 2, and gamma 2L 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 GABA(A) 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 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 within the endoplasmic reticulum. These results suggest that receptor assembly occurs by defined pathways, which may serve to limit the diversity of GABA(A) receptors that exist on the surface of neurons.",
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    Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors. / Connolly, Christopher N.; Krishek, Belinda J. ; McDonald, Bernard J. ; Smart, Trevor G.; Moss, Stephen J.

    In: Journal of Biological Chemistry, Vol. 271, No. 1, 05.01.1996, p. 89-96.

    Research output: Contribution to journalArticle

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    AU - Connolly, Christopher N.

    AU - Krishek, Belinda J.

    AU - McDonald, Bernard J.

    AU - Smart, Trevor G.

    AU - Moss, Stephen J.

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    AB - The ability of differing subunit combinations of gamma-aminobutyric acid type A (GABA(A)) receptors produced from murine alpha 1, beta 2, and gamma 2L 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 GABA(A) 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 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 within the endoplasmic reticulum. These results suggest that receptor assembly occurs by defined pathways, which may serve to limit the diversity of GABA(A) receptors that exist on the surface of neurons.

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