Biochemical and biophysical evidence for γ2 subunit association with neuronal voltage-activated Ca2+ channels
Biochemical and biophysical evidence for γ2 subunit association with neuronal voltage-activated Ca2+ channels
复制标题
DOI：
10.1074/jbc.m100787200
复制
发表时间：
2001-08-31
影响因子：
4.8
通讯作者：
Campbell, KP
中科院分区：
文献类型：
--
作者：
Kang, MG;Chen, CC;Campbell, KP
一个新的基因(Cacng2；Gamma(2))编码一种类似于电压激活的钙通道伽马(1)亚单位的蛋白质，在癫痫和共济失调小鼠Stargazer中被鉴定为缺陷基因。在这项研究中，我们分析了这个新的神经元γ(2)亚基与兔脑钙通道的关系，以及在非洲爪哇卵母细胞中表达的重组神经元钙通道中的功能。我们的结果表明，在体内，伽马(2)亚基和一种密切相关的蛋白质(称为伽马(3))与神经元钙通道亚基共沉淀和免疫共沉淀。电生理分析表明，y2共表达导致α(1B)(α(1)2.2)类(36.8%)和α(1A)(α(1)2.1)类(39.7%)钙通道(α(1)β(3)α(2)Delta)的电流幅度显著降低。有趣的是，γ(2)亚基对电流幅度的抑制作用依赖于α(2)β亚基的共表达。此外，γ(2)或γ(1)的共同表达也显著减慢了IB类钙通道的激活动力学。综上所述，这些结果表明，γ(2)亚单位是神经元钙通道复合体的重要组成部分，它下调神经元钙通道的活性。此外，伽马(2)亚基可能通过抵消α(2)增量亚基的影响而对神经元钙通道的微调做出贡献。
A novel gene (Cacng2; gamma (2)) encoding a protein similar to the voltage-activated Ca2+ channel gamma (1) subunit was identified as the defective gene in the epileptic and ataxic mouse, stargazer. In this study, we analyzed the association of this novel neuronal gamma (2) subunit with Ca2+ channels of rabbit brain, and the function of the gamma (2) subunit in recombinant neuronal Ca2+ channels expressed in Xenopus oocytes. Our results showed that the gamma (2) subunit and a closely related protein (called gamma (3)) co-sedimented and co-immunoprecipitated with neuronal Ca2+ channel subunits in vivo. Electrophysiological analyses showed that y2 co-expression caused a significant decrease in the current amplitude of both alpha (1B)(alpha (1)2.2)-class (36.8%) and alpha (1A)(alpha (1)2.1)-class (39.7%) Ca2+ channels (alpha (1)beta (3)alpha (2)delta)- Interestingly, the inhibitory effects of the gamma (2) subunit on current amplitude were dependent on the co-expression of the alpha (2)delta subunit. In addition, co-expression of gamma (2) or gamma (1) also significantly decelerates the activation kinetics of a IB-class Ca2+ channels. Taken together, these results suggest that the gamma (2) subunit is an important constituent of the neuronal Ca2+ channel complex and that it down-regulates neuronal Ca2+ channel activity. Furthermore, the gamma (2) subunit likely contributes to the fine-tuning of neuronal Ca2+ channels by counterbalancing the effects of the alpha (2)delta subunit.