Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1
Differential modulation of Cav2.1 channels by calmodulin and Ca2+-binding protein 1
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DOI：
10.1038/nn805
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发表时间：
2002-03-01
影响因子：
25
通讯作者：
Catterall, WA
中科院分区：
文献类型：
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作者：
Lee, A;Westenbroek, RE;Catterall, WA
介导P/Q型钙电流的Ca(V)2.1通道经历钙/钙调蛋白(CaM)依赖的失活和易化，可显著改变突触效应。在这里，我们报道了神经元钙结合蛋白1(CaBP1)对Ca(V)2.1通道的调制方式与CaM的调制方式明显不同。CaBP1增强失活，引起电压依赖性激活的去极化转变，不支持钙依赖的Ca(V)2.1通道的易化。CaBP1的这些抑制作用不需要钙离子，但依赖于Ca(V)2.1通道(α(1)2.1)的α(1)亚单位中的CaM结合结构域。CaBP1与CaM结合域结合，与来自转基因细胞和脑提取液的α(1)2.1免疫共沉淀，并与α(1)2.1共存于海马神经元和小脑神经元的离散微域。我们的结果证实了钙通道和CaBP1之间的相互作用，可能通过抑制钙内流来调节钙依赖的突触可塑性。
Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM) dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha(1) subunit of Ca(v)2.1 channels (alpha(1)2.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha(1)2.1 from transfected cells and brain extracts, and colocalizes with alpha(1)2.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.