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首页> 外文期刊>Journal of Receptor, Ligand and Channel Research >Nedd4-2 regulation of voltage-gated ion channels: an update on structure–function relationships and the pathophysiological consequences of dysfunction
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Nedd4-2 regulation of voltage-gated ion channels: an update on structure–function relationships and the pathophysiological consequences of dysfunction

机译：Nedd4-2电压门控离子通道的调节：结构-功能关系和功能障碍的病理生理后果的更新

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Abstract: Neuronal excitability is mediated mainly by voltage-gated ion channels (VGICs), which include voltage-gated Na+, K+, and Cl– channels located along the axon and at neuronal synapses. Voltage-gated channels play pivotal roles in the proper functioning of the nervous system because they set the resting membrane potential, initiate and propagate action potentials, and regulate neurotransmitter release. The abnormal activity or misregulation of VGICs caused by mutations has been directly linked to neurological and cardiac diseases. Among other posttranslational modifications, the ubiquitination of VGICs is a key to the regulation of the number of channels in the cell surface, and hence, neuronal excitability. Nedd4-2 is an E3 ubiquitin ligase that ubiquitinates several proteins, including different VGICs. Accordingly, understanding the molecular mechanisms underlying channel regulation will provide insights to design drugs to treat illnesses. The focus of the present review is to provide an update about the regulation of VGICs upon ubiquitination by Nedd4-2 and the relevance of such regulation in the pathophysiological consequences of dysfunction.
机译：摘要：神经元的兴奋性主要由电压门控离子通道（VGIC）介导，其中包括沿轴突和神经突触处的电压门控Na +，K +和Cl–通道。电压门控通道在神经系统的正常功能中起着关键作用，因为它们设置了静息膜电位，启动并传播了动作电位并调节了神经递质的释放。由突变引起的VGIC的异常活动或调节异常与神经系统疾病和心脏病直接相关。在其他翻译后修饰中，VGIC的泛素化是调节细胞表面通道数量以及神经元兴奋性的关键。 Nedd4-2是一种E3泛素连接酶，可泛素化几种蛋白质，包括不同的VGIC。因此，了解通道调节的分子机制将为设计治疗疾病的药物提供见识。本综述的重点是提供有关Nedd4-2泛素化后VGICs调控的最新进展，以及这种调控在功能障碍的病理生理后果中的相关性。

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