Abstract:
Neuronal nicotinic acetylcholine receptors (nAChRs) are a family of pentameric, ligand-gated ion channels that are located on the surface of neurons and non-neuronal cells and have multiple physiological and pathophysiological functions. In order to reach the cell surface, many nAChR subtypes require the help of chaperone and/or auxiliary/accessory proteins for their assembly, trafficking, pharmacological modulation, and normal functioning in vivo. The use of powerful genome-wide cDNA screening has led to the identification and characterisation of the molecules and mechanisms that participate in the assembly and trafficking of receptor subtypes, including chaperone and auxiliary or accessory proteins. The aim of this review is to describe the latest findings concerning nAChR chaperones and auxiliary proteins and pharmacological chaperones, and how some of them control receptor biogenesis or regulate channel activation and pharmacology. Some auxiliary proteins are subtype selective, some regulate various subtypes, and some not only modulate nAChRs but also target other receptors and signalling pathways. We also discuss how changes in auxiliary proteins may be involved in nAChR dysfunctions.
摘要:
神经元烟碱乙酰胆碱受体(nAChRs)是一个五聚体家族,配体门控离子通道,位于神经元和非神经元细胞表面,具有多种生理和病理生理功能。为了到达细胞表面,许多nAChR亚型需要伴侣和/或辅助/辅助蛋白的帮助来组装,贩运,药理学调制,和体内正常功能。强大的全基因组cDNA筛选的使用导致了参与受体亚型组装和运输的分子和机制的鉴定和表征,包括伴侣和辅助或辅助蛋白。这篇综述的目的是描述有关nAChR伴侣和辅助蛋白以及药理伴侣的最新发现,以及它们中的一些如何控制受体生物发生或调节通道激活和药理学。一些辅助蛋白具有亚型选择性,一些调节各种亚型,有些不仅调节nAChRs,而且还靶向其他受体和信号通路。我们还讨论了辅助蛋白的变化可能与nAChR功能障碍有关。