Foreword: trafficking, assembly and regulation of neurotransmitter receptors and ion channels.
Foreword: trafficking, assembly and regulation of neurotransmitter receptors and ion channels.
复制标题
前言：神经递质受体和离子通道的运输、组装和调节。
DOI：
10.1080/09687680802060665
复制
发表时间：
2008
影响因子：
--
通讯作者：
Stephenson FA
中科院分区：
文献类型：
--
作者：
Stephenson FA
一般来说，神经元细胞网络之间的通信是不连续的，并通过相邻神经元的专门区域（突触）发生。在这里，神经递质从激活的神经元释放并扩散穿过突触间隙，以结合到接收细胞树突中突触后膜中的同源神经递质受体。因此，神经冲动的通讯和传播至关重要，取决于配体门控（也称为离子型）和G蛋白偶联（代谢型）神经递质受体以及电压门控离子通道在这些区域的适当定位。通常，离子型受体主要分布在突触后膜的突触或突触外位点，但它们也存在于突触前膜中，并以较低浓度存在于其他特定的神经元膜隔室，如轴突丘。电压门控离子通道在突触后和突触前膜内以及在沿着神经轴突的限定区域也具有特定的亚细胞分布，这取决于它们的专门功能。虽然有树突中局部蛋白质合成的例子，但大多数蛋白质合成主要发生在神经元细胞体内，因此这些离子通道必须被运输到其适当的目的地。离子型受体和电压门控离子通道都是多亚基、异聚体、整合的膜蛋白。此外，对于每种类型的受体和电压门控离子通道，存在多种基因，导致每个蛋白质家族的广泛异质性。因此，神经元需要使用在内质网（ER）中操作的初级和次级质量控制机制，正确的亚基组合被组装，然后通过分泌途径向前运输到质膜的适当子域。配体门控神经递质受体和电压门控神经递质受体的亚基组成，门控离子通道在某种程度上受基因转录控制，但越来越明显的是，特定的神经元细胞类型可以表达相同受体或离子通道家族的多种亚型。这些具有不同功能特性的亚型通常针对特定的定位。这意味着神经元具有复杂的机制，涉及多种蛋白质-蛋白质相互作用，用于通常高度同源的蛋白质的运输和分选，以确保适当数量的通道在正常神经元功能的正确隔室中表达。发表在《分子膜生物学》特刊上的一系列综述文章将描述我们目前对离子型神经递质受体和电压门控钾通道的生物起源的理解。
In general, communication between networks of neuronal cells is non-continuous and occurs via specialized regions of adjacent neurones, the synapses. Here neurotransmitters are released from an activated neurone and diffuse across the synaptic cleft to bind to their cognate neurotransmitter receptor in the post-synaptic membrane in the dendrites of the receiving cell. The communication and propagation of nerve impulses is thus crucially dependent upon the appropriate localization to these zones of both ligand-gated (also termed ionotropic) and G-protein coupled (metabotropic) neurotransmitter receptors and, voltage-gated ion channels. Generally, ionotropic receptors are mostly distributed in the post-synaptic membrane at either synaptic or extra-synaptic sites but they are also found in presynaptic membranes and at lower concentrations, at other specific neuronal membrane compartments such as at the axon hillock. Voltage-gated ion channels also have specific subcellular distributions within post-synaptic and pre-synaptic membranes and also, at defined regions along the nerve axons depending upon their specialized functions. Although there are examples of local protein synthesis in dendrites, the majority of protein synthesis occurs mostly within neuronal cell bodies thus these ion channels must be trafficked to their appropriate destinations. Both ionotropic receptors and the voltage-gated ion channels are multi-subunit, heteromeric, integral membrane proteins. Further for each type of receptor and voltage-gated ion channel, there exists a multiplicity of genes giving rise to extensive heterogeneity for each family of proteins. Thus neurones need to ensure, using primary and secondary quality control mechanisms that operate in the endoplasmic reticulum (ER), that the correct subunit combinations are assembled and then forward trafficked via the secretory pathway to the appropriate sub-domain of the plasma membrane.The subunit composition of ligand-gated neurotransmitter receptors and voltage-gated ion channels is to some extent controlled by gene transcription but it is increasingly apparent that a specific neuronal cell type can express multiple subtypes of the same receptor or ion channel family. These subtypes with distinct functional properties are often targeted to specific localizations. This implies that neurones possess a sophisticated machinery involving multiple protein-protein interactions for the trafficking and sorting of often highly homologous proteins to ensure that appropriate numbers of channels are expressed in the correct compartments for normal neuronal function. The series of review articles published here in this special issue of Molecular Membrane Biology, will describe our current understanding of the biogenesis of ionotropic neurotransmitter receptors and the voltage-gated potassium channels.