Excitation Control: Balancing PSD-95 Function at the Synapse.

Excitation Control: Balancing PSD-95 Function at the Synapse.
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DOI:
10.3389/neuro.02.004.2008
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发表时间:
2008
影响因子:
4.8
通讯作者:
El-Husseini, Alaa
El-Husseini, Alaa
中科院分区:
医学2区
文献类型:
--
作者:
Keith, Dove;El-Husseini, Alaa

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单个神经元的兴奋性决定了特定脑回路的整体兴奋程度。这一过程被认为是由调节突触数量、形态和强度的分子调控的。神经元兴奋也受保留在特定突触位点的神经递质受体和信号分子数量的影响。最近的研究表明,PSD-95作为谷氨酸能突触上富集的一种支架分子,在突触后位点调节几种神经递质受体、粘附分子、离子通道、细胞骨架元件和信号分子的聚集中起着关键作用。在这篇综述中,我们将重点介绍PSD-95在突触上的靶向控制机制,并讨论该分子如何影响不同突触蛋白的保留和聚集,从而调节突触的结构和强度。我们还将讨论PSD-95如何在大脑中维持兴奋和抑制之间的平衡,以及这种平衡的改变如何导致神经精神疾病。
Excitability of individual neurons dictates the overall excitation in specific brain circuits. This process is thought to be regulated by molecules that regulate synapse number, morphology and strength. Neuronal excitation is also influenced by the amounts of neurotransmitter receptors and signaling molecules retained at particular synaptic sites. Recent studies revealed a key role for PSD-95, a scaffolding molecule enriched at glutamatergic synapses, in modulation of clustering of several neurotransmitter receptors, adhesion molecules, ion channels, cytoskeletal elements and signaling molecules at postsynaptic sites. In this review we will highlight mechanisms that control targeting of PSD-95 at the synapse, and discuss how this molecule influences the retention and clustering of diverse synaptic proteins to regulate synaptic structure and strength. We will also discuss how PSD-95 may maintain a balance between excitation and inhibition in the brain and how alterations in this balance may contribute to neuropsychiatric disorders.
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