Molecular Diversity of the Calcium Channel α2δ Subunit

Molecular Diversity of the Calcium Channel α2δ Subunit
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钙通道α2δ亚基的分子多样性

DOI:
10.1523/jneurosci.19-02-00684.1999
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发表时间:
1999
期刊:
The Journal of Neuroscience
影响因子:
--
通讯作者:
F. Hofmann
F. Hofmann
中科院分区:
--
文献类型:
--
作者:
N. Klugbauer;Ľ. Lacinová;E. Marais;M. Hobom;F. Hofmann

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使用 α2δ 亚基作为探针进行序列数据库搜索,鉴定出编码具有该钙通道亚基基本特性的蛋白质的两个新基因。一级结构比较表明,新的α2δ-2和α2δ-3亚基与α2δ-1亚基分别具有55.6%和30.3%的同一性。 α2δ-3 亚基的假定糖基化位点和半胱氨酸残基的数量、亲水性特征和电生理特征表明这些蛋白质是功能性钙通道亚基。 α2δ-3与α1C和心脏β2a或α1E和β3亚基的共表达将通道激活和失活的电压依赖性向超极化方向转变,并加速了电流失活的动力学。仅当α2δ-1或α2δ-3与α1C一起表达时,电流激活的动力学才会改变。 α2δ-3 对 α1C 但对 α1E 的影响与 α2δ-1 的影响无法区分。使用 Northern 印迹分析表明,α2δ-3 仅在大脑中表达,而 α2δ-2 在多种组织中发现。小鼠脑切片的原位杂交显示,海马、小脑和皮质中存在α2δ-1和α2δ-3的mRNA表达,其中在嗅球中强烈检测到α2δ-1,在尾壳核中强烈检测到α2δ-3。
Sequence database searches with the α2δ subunit as probe led to the identification of two new genes encoding proteins with the essential properties of this calcium channel subunit. Primary structure comparisons revealed that the novel α2δ-2 and α2δ-3 subunits share 55.6 and 30.3% identity with the α2δ-1 subunit, respectively. The number of putative glycosylation sites and cysteine residues, hydropathicity profiles, and electrophysiological character of the α2δ-3 subunit indicates that these proteins are functional calcium channel subunits. Coexpression of α2δ-3 with α1C and cardiac β2a or α1E and β3 subunits shifted the voltage dependence of channel activation and inactivation in a hyperpolarizing direction and accelerated the kinetics of current inactivation. The kinetics of current activation were altered only when α2δ-1 or α2δ-3 was expressed with α1C. The effects of α2δ-3 on α1C but not α1E are indistinguishable from the effects of α2δ-1. Using Northern blot analysis, it was shown that α2δ-3 is expressed exclusively in brain, whereas α2δ-2 is found in several tissues. In situ hybridization of mouse brain sections showed mRNA expression of α2δ-1 and α2δ-3 in the hippocampus, cerebellum, and cortex, with α2δ-1 strongly detected in the olfactory bulb and α2δ-3 in the caudate putamen.
非洲爪蟾卵母细胞中 α2/δ 和 β 亚基对 Ca2 电流的增强:通道门控和 α1 蛋白水平变化的贡献。
DOI: 10.1113/jphysiol.1995.sp021029
发表时间: 1995
期刊: The Journal of physiology
影响因子: --
作者:
Shistik,E;Ivanina,T;Puri,T;Hosey,M;Dascal,N
通讯作者: Dascal,N