Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors
Assembly and cell surface expression of heteromeric and homomeric gamma-aminobutyric acid type A receptors
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DOI：
10.1074/jbc.271.1.89
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发表时间：
1996-01-05
影响因子：
4.8
通讯作者：
Moss, SJ
中科院分区：
文献类型：
--
作者：
Connolly, CN;Krishek, BJ;Moss, SJ
使用分子、电生理、生物化学和形态学方法的组合，在A293细胞和爪蟾卵母细胞中分析了由鼠α 1、β 2和γ 2L亚基产生的γ-氨基丁酸A型（GABA（A））受体的不同亚基组合形成功能性细胞表面受体的能力。结果表明，GABA（A）受体在内质网内组装，并与分子伴侣、免疫球蛋白重链结合蛋白和钙连接蛋白相互作用。尽管所有三个亚基都具有彼此寡聚化的能力，但只有α 1 β 2和α 1 β 2 γ 2L亚基组合可以在不依赖于N-连接糖基化的过程中产生功能性表面表达。单个亚基和α 1 γ 2L和β 2 γ 2L组合保留在内质网内。这些结果表明，受体组装发生通过确定的途径，这可能有助于限制GABA（A）受体的多样性，存在于神经元表面。
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.