Dual function of the voltage-dependent Ca2+ channel alpha(2)delta subunit in current stimulation and subunit interaction
Dual function of the voltage-dependent Ca2+ channel alpha(2)delta subunit in current stimulation and subunit interaction
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DOI：
10.1016/s0896-6273(00)80061-6
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发表时间：
1996-02-01
期刊：
影响因子：
16.2
通讯作者：
Campbell, KP
中科院分区：
文献类型：
--
作者：
Gurnett, CA;DeWaard, M;Campbell, KP
电压依赖性Ca 2+通道通过与α（2）δ亚基的复杂相互作用来调节。体外翻译用于证明α（2）δ亚基的单一跨膜拓扑结构，其中除跨膜序列和5个羧基末端氨基酸外，所有其他均位于细胞外。糖基化的细胞外结构域是电流刺激所必需的，如在非洲爪蟾卵母细胞中截短的α（2）δ亚基与α（1A）和β（4）亚基的共表达以及用肽-N-糖苷酶F去糖基化所示。然而，含有跨膜结构域的δ亚基的共表达降低了全长α（2）δ亚基的刺激作用，并且不同跨膜结构域的取代导致电流刺激的损失。这些结果支持了一种模型，其中α（2）δ跨膜结构域介导亚基相互作用和糖基化的细胞外结构域增强电流幅度。
Voltage-dependent Ca2+ channels are modulated by complex interactions with the alpha(2) delta subunit. In vitro translation was used to demonstrate a single transmembrane topology of the alpha(2) delta subunit in which all but the transmembrane sequence and 5 carboxy-terminal amino acids are extracellular. The glycosylated extracellular domain is required for current stimulation, as shown by coexpression of truncated alpha(2) delta subunits with alpha(1A) and beta(4) subunits in Xenopus oocytes and deglycosylation with peptide-N-glycosidase F. However, coexpression of the transmembrane domain-containing delta subunit reduced the stimulatory effects of full-length alpha(2) delta subunits and substitution of a different transmembrane domain resulted in a loss of current stimulation. These results support a model whereby the alpha(2) delta transmembrane domain mediates subunit interactions and the glycosylated extracellular domain enhances current amplitude.