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涉及神经元烟碱型乙酰胆碱受体表达和功能的蛋白质和化学伴侣:最新进展。

Proteins and chemical chaperones involved in neuronal nicotinic receptor expression and function: an update.

机构信息

CNR, Institute of Neuroscience, Milan, Italy.

出版信息

Br J Pharmacol. 2018 Jun;175(11):1869-1879. doi: 10.1111/bph.13777. Epub 2017 Apr 19.

Abstract

UNLABELLED

Neuronal nicotinic ACh receptors (nAChRs) are a family of ACh-gated cation channels, and their homeostasis or proteostasis is essential for the correct physiology of the central and peripheral nervous systems. The proteostasis network regulates the folding, assembly, degradation and trafficking of nAChRs in order to ensure their efficient and functional expression at the cell surface. However, as nAChRs are multi-subunit, multi-span, integral membrane proteins, the folding and assembly is a very inefficient process, and only a small proportion of subunits can form functional pentamers. Moreover, the efficiency of assembly and trafficking varies widely depending on the nAChR subtypes and the cell type in which they are expressed. A detailed understanding of the mechanisms that regulate the functional expression of nAChRs in neurons and non-neuronal cells is therefore important. The purpose of this short review is to describe more recent findings concerning the chaperone proteins and target-specific and target-nonspecific pharmacological chaperones that modulate the expression of nAChR subtypes, and the possible mechanisms that underlie the dynamic changes of cell surface nAChRs.

LINKED ARTICLES

This article is part of a themed section on Nicotinic Acetylcholine Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

摘要

未加标签

神经元烟碱型乙酰胆碱受体 (nAChRs) 是一类 ACh 门控阳离子通道,其内稳态或蛋白平衡对于中枢和外周神经系统的正常生理功能至关重要。蛋白平衡网络调节 nAChRs 的折叠、组装、降解和转运,以确保其在细胞表面的有效和功能性表达。然而,由于 nAChRs 是多亚基、多跨膜、整合膜蛋白,折叠和组装是一个非常低效的过程,只有一小部分亚基可以形成功能性五聚体。此外,组装和转运的效率因 nAChR 亚型和表达它们的细胞类型而异而有很大差异。因此,详细了解调节神经元和非神经元细胞中 nAChRs 功能性表达的机制非常重要。本文的目的是描述最近关于伴侣蛋白和针对特定靶标及非特定靶标的药理学伴侣蛋白的发现,这些伴侣蛋白调节 nAChR 亚型的表达,以及细胞表面 nAChRs 动态变化的潜在机制。

相关文章

本文是关于烟碱型乙酰胆碱受体的专题部分的一部分。要查看本部分的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.11/issuetoc.

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