Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases
Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases
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DOI：
10.1007/s11064-012-0886-y
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
de Bartolomeis, Andrea
中科院分区：
文献类型：
--
作者：
Iasevoli, Felice;Tomasetti, Carmine;de Bartolomeis, Andrea
突触可塑性是指与活动相关的突触传递的长期增强或减弱，其典型类型为长期增强和长期抑制。尽管有这个经典的定义，然而，突触可塑性发生的分子机制似乎是极其复杂和多样的。谷氨酸能突触的突触后密度（PSD）是突触可塑性过程的主要位点，PSD成员的改变最近与神经精神疾病有关，其中突触可塑性损伤也有报道。在PSD成员中，支架蛋白已被证明可以桥接表面受体及其细胞内效应物，并调节受体在表面膜和PSD内的分布和定位。本文将对突触可塑性过程的分子生理学和病理生理学进行综述，该过程是由支架PSD蛋白及其密切相关伙伴通过调节突触后位点的受体定位和分布来调节的。我们认为，通过调节受体沿表面膜的区隔化及其降解，以及调节受体转运到PSD，突触后支架蛋白可能有助于形成不同的信号微结构域，其传递突触信号的有效性取决于支架的动态稳定性，而这反过来又由支架成员的相对数量和翻译后修饰提供。在本工作的最后一部分讨论了与神经精神疾病的推定相关性和可能的病理生理机制。
Synaptic plasticity represents the long lasting activity-related strengthening or weakening of synaptic transmission, whose well-characterized types are the long term potentiation and depression. Despite this classical definition, however, the molecular mechanisms by which synaptic plasticity may occur appear to be extremely complex and various. The post-synaptic density (PSD) of glutamatergic synapses is a major site for synaptic plasticity processes and alterations of PSD members have been recently implicated in neuropsychiatric diseases where an impairment of synaptic plasticity has also been reported. Among PSD members, scaffolding proteins have been demonstrated to bridge surface receptors with their intracellular effectors and to regulate receptors distribution and localization both at surface membranes and within the PSD. This review will focus on the molecular physiology and pathophysiology of synaptic plasticity processes, which are tuned by scaffolding PSD proteins and their close related partners, through the modulation of receptor localization and distribution at post-synaptic sites. We suggest that, by regulating both the compartmentalization of receptors along surface membrane and their degradation as well as by modulating receptor trafficking into the PSD, postsynaptic scaffolding proteins may contribute to form distinct signaling micro-domains, whose efficacy in transmitting synaptic signals depends on the dynamic stability of the scaffold, which in turn is provided by relative amounts and post-translational modifications of scaffolding members. The putative relevance for neuropsychiatric diseases and possible pathophysiological mechanisms are discussed in the last part of this work.