Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences.
Alternative splicing: functional diversity among voltage-gated calcium channels and behavioral consequences.
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DOI：
10.1016/j.bbamem.2012.09.018
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发表时间：
2013-07
影响因子：
3.4
通讯作者：
Allen, Summer E.
中科院分区：
文献类型：
--
作者：
Lipscombe, Diane;Andrade, Arturo;Allen, Summer E.
关键词：
神经元电压门控钙通道响应于膜去极化而产生快速、瞬时的细胞内钙信号。神经元CaV通道调节一系列细胞功能，并且涉及多种神经和精神疾病，包括癫痫、帕金森病、慢性疼痛、精神分裂症和双相情感障碍。每个哺乳动物Cacna1基因都有可能通过选择性前体mRNA剪接产生数万至数千个CaV通道，这是一个向CaV通道结构和功能库添加细颗粒的过程。在每个细胞中表达的CaV通道剪接异构体mRNA的精确组成由细胞特异性剪接因子控制。剪接因子的活性又受到编码各种细胞特征的分子的调节，所述细胞特征包括细胞类型、活性、代谢状态、发育状态和其他因子。CaV剪接异构体的各个位点的细胞和行为后果正在阐明，作为控制剪接异构体选择的细胞特异性剪接因子。CaV前体mRNA可变剪接模式的改变可以以微妙但可测量的方式改变行为，并可能影响药物疗效和疾病严重程度。这篇文章是一个特殊问题的一部分，题为：钙通道。
Neuronal voltage-gated calcium channels generate rapid, transient intracellular calcium signals in response to membrane depolarization. Neuronal CaV channels regulate a range of cellular functions and are implicated in a variety of neurological and psychiatric diseases including epilepsy, Parkinson’s disease, chronic pain, schizophrenia, and bipolar disorder. Each mammalian Cacna1 gene has the potential to generate tens to thousands of CaV channels by alternative pre-mRNA splicing, a process that adds fine granulation to the pool of CaV channel structures and functions. The precise composition of CaV channel splice isoform mRNAs expressed in each cell are controlled by cell-specific splicing factors. The activity of splicing factors are in turn regulated by molecules that encode various cellular features, including cell-type, activity, metabolic states, developmental state, and other factors. The cellular and behavioral consequences of individual sites of CaV splice isoforms are being elucidated, as are the cell-specific splicing factors that control splice isoform selection. Altered patterns of alternative splicing of CaV pre-mRNAs can alter behavior in subtle but measurable ways, with the potential to influence drug efficacy and disease severity. This article is part of a Special Issue entitled: Calcium channels.
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