Alternative Splicing of L-type Ca(V)1.2 Calcium Channels: Implications in Cardiovascular Diseases.
Alternative Splicing of L-type Ca(V)1.2 Calcium Channels: Implications in Cardiovascular Diseases.
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DOI：
10.3390/genes8120344
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发表时间：
2017-11-24
期刊：
影响因子：
3.5
通讯作者：
Soong TW
中科院分区：
文献类型：
--
作者：
Hu Z;Liang MC;Soong TW
l型CaV1.2钙通道是Ca2+内流启动平滑肌和心肌收缩的主要途径。CaV1.2通道功能的改变与多种心血管疾病有关，如高血压和心脏肥厚。选择性剪接是一种转录后机制，可扩展CaV1.2通道结构，以改变功能、药理学和生物物理性质，如钙/电压依赖性失活（C/VDI），或通过相互作用蛋白（如半乳糖凝素-1）影响其翻译后调节。选择性剪接产生了功能多样的CaV1.2亚型，这些亚型可以在心脏或心力衰竭等病理生理条件下进行发育调节。更重要的是，CaV1.2某些外显子的选择性剪接已被报道由剪接因子如rna结合Fox-1同源物1/2 （Rbfox 1/2）、聚嘧啶束结合蛋白（PTBP1）和rna结合基序蛋白20 （RBM20）调节。了解CaV1.2通道功能在疾病中的重塑将提供更好的信息，指导开发更有针对性的方法来发现心血管疾病的治疗药物。
L-type CaV1.2 calcium channels are the major pathway for Ca2+ influx to initiate the contraction of smooth and cardiac muscles. Alteration of CaV1.2 channel function has been implicated in multiple cardiovascular diseases, such as hypertension and cardiac hypertrophy. Alternative splicing is a post-transcriptional mechanism that expands CaV1.2 channel structures to modify function, pharmacological and biophysical property such as calcium/voltage-dependent inactivation (C/VDI), or to influence its post-translational modulation by interacting proteins such as Galectin-1. Alternative splicing has generated functionally diverse CaV1.2 isoforms that can be developmentally regulated in the heart, or under pathophysiological conditions such as in heart failure. More importantly, alternative splicing of certain exons of CaV1.2 has been reported to be regulated by splicing factors such as RNA-binding Fox-1 homolog 1/2 (Rbfox 1/2), polypyrimidine tract-binding protein (PTBP1) and RNA-binding motif protein 20 (RBM20). Understanding how CaV1.2 channel function is remodelled in disease will provide better information to guide the development of more targeted approaches to discover therapeutic agents for cardiovascular diseases.
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DOI：
10.1073/pnas.89.4.1497
发表时间：
1992-02-15
影响因子：
11.1
作者：
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