The C terminus of the L-type voltage-gated calcium channel Cav1.2 encodes a transcription factor
The C terminus of the L-type voltage-gated calcium channel Cav1.2 encodes a transcription factor
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DOI：
10.1016/j.cell.2006.10.017
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发表时间：
2006-11-03
期刊：
影响因子：
64.5
通讯作者：
Dolmetsch, Ricardo
中科院分区：
文献类型：
--
作者：
Gomez-Ospina, Natalia;Tsuruta, Fuminori;Dolmetsch, Ricardo
电压门控钙通道在调节神经元和肌肉细胞的电和生物化学性质中起着核心作用。钙通道调节持久神经元特性的方式之一是通过激活控制基因表达的信号通路，但将钙通道连接到细胞核的机制尚不清楚。我们报告了Ca（v）1.2（L型电压门控钙通道（LTC））的C端片段易位到细胞核并调节转录。我们表明，这种钙通道相关转录调节因子（CCAT）与核蛋白结合，与内源性启动子结合，并调节对神经元信号传导和兴奋性重要的多种内源性基因的表达。CCAT的核定位受发育和细胞内钙变化的调节。这些发现提供了证据，电压门控钙通道可以直接激活转录，并提出了一种机制，连接电压门控通道的功能和兴奋细胞的分化。
Voltage-gated calcium channels play a central role in regulating the electrical and biochemical properties of neurons and muscle cells. One of the ways in which calcium channels regulate long-lasting neuronal properties is by activating signaling pathways that control gene expression, but the mechanisms that link calcium channels to the nucleus are not well understood. We report that a C-terminal fragment of Ca(v)1.2, an L-type voltage-gated calcium channel (LTC), translocates to the nucleus and regulates transcription. We show that this calcium channel associated transcription regulator (CCAT) binds to a nuclear protein, associates with an endogenous promoter, and regulates the expression of a wide variety of endogenous genes important for neuronal signaling and excitability. The nuclear localization of CCAT is regulated both developmentally and by changes in intracellular calcium. These findings provide evidence that voltage-gated calcium channels can directly activate transcription and suggest a mechanism linking voltage-gated channels to the function and differentiation of excitable cells.