Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels
Alternative splicing as a molecular switch for Ca2+/calmodulin-dependent facilitation of P/Q-type Ca2+ channels
复制标题
DOI：
10.1523/jneurosci.1712-04.2004
复制
发表时间：
2004-07-14
影响因子：
5.3
通讯作者：
Yue, DT
中科院分区：
文献类型：
--
作者：
Chaudhuri, D;Chang, SY;Yue, DT
P/Q-型通道（Ca（V）2.1）的选择性剪接承诺神经元计算库的定制。在这里，我们报告，其主要的α（1A）亚基，在EF-手样结构域和通道C末端的协同剪接，控制Ca 2+依赖性易化（CDF）的形式，钙调蛋白触发的通道开放的活性依赖性增强。在重组通道中，这种选择性剪接在三种模式中切换CDF：（1）完全“开启”并由通过单个通道的局部Ca 2+内流驱动，（2）完全“关闭”，以及（3）部分关闭但可由升高的整体Ca 2+内流诱导。从模式1到模式3的转变是前所未有的控制层面。这些变体的生理功能可能很重要，因为我们发现EF-手剪接变体在人脑中的分布是惊人的异质性，在不同区域和发育过程中都有差异。
Alternative splicing of the P/Q-type channel (Ca(V)2.1) promises customization of the computational repertoire of neurons. Here we report that concerted splicing of its main alpha(1A) subunit, at both an EF-hand-like domain and the channel C terminus, controls the form of Ca2+-dependent facilitation (CDF), an activity-dependent enhancement of channel opening that is triggered by calmodulin. In recombinant channels, such alternative splicing switches CDF among three modes: ( 1) completely "ON" and driven by local Ca2+ influx through individual channels, ( 2) completely "OFF," and ( 3) partially OFF but inducible by elevated global Ca2+ influx. Conversion from modes 1 to 3 represents an unprecedented dimension of control. The physiological function of these variants is likely important, because we find that the distribution of EF-hand splice variants is strikingly heterogeneous in the human brain, varying both across regions and during development.