Stephenson F Anne, Cousins Sarah L, Kenny Anna V
School of Pharmacy, University of London, London, UK.
Mol Membr Biol. 2008 May;25(4):311-20. doi: 10.1080/09687680801971367.
N-Methyl-D-aspartate (NMDA) receptors are a subclass of the excitatory, ionotropic L-glutamate neurotransmitter receptors. They are important for normal brain function being both primary candidates for the molecular basis of learning and memory and in the establishment of synaptic connections during the development of the central nervous system. NMDA receptors are also implicated in neurological and psychiatric disorders. Their dysfunction which is primarily due to either hypo- or hyper-activity is pivotal to these pathological conditions. There is thus a fine balance between NMDA receptor-mediated mechanisms in normal brain and those in diseased states where receptor homeostasis is perturbed. Receptor activity is due in part to the number of surface expressed receptors. Understanding the assembly and trafficking of this complex, heteromeric, neurotransmitter receptor family may therefore, be pivotal to understanding diseases in which their altered activity is evident. This article will review the current understanding of the mechanisms of NMDA receptor assembly, how this assembly is regulated and how assembled receptors are trafficked to their appropriate sites in post-synaptic membranes where they are integral components of a macromolecular signalling complex.
N-甲基-D-天冬氨酸(NMDA)受体是兴奋性离子型L-谷氨酸神经递质受体的一个亚类。它们对正常脑功能很重要,既是学习和记忆分子基础的主要候选者,也是中枢神经系统发育过程中突触连接建立的关键因素。NMDA受体还与神经和精神疾病有关。其功能障碍主要由于活性过低或过高,这对这些病理状况至关重要。因此,在正常大脑中NMDA受体介导的机制与受体稳态受到干扰的疾病状态之间存在着微妙的平衡。受体活性部分归因于表面表达的受体数量。因此,了解这个复杂的异聚神经递质受体家族的组装和运输,对于理解其活性改变明显的疾病可能至关重要。本文将综述目前对NMDA受体组装机制的理解、这种组装如何被调控,以及组装好的受体如何被运输到突触后膜的适当位置,在那里它们是大分子信号复合物的组成部分。