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Fractional occupancy of synaptic binding sites and the molecular plasticity of inhibitory synapses.
Neuropharmacology ( IF 4.6 ) Pub Date : 2019-01-12 , DOI: 10.1016/j.neuropharm.2019.01.008
Christian G Specht 1
Affiliation  

The postsynaptic density (PSD) at inhibitory synapses is a complex molecular assembly that serves as a platform for the interaction of neurotransmitter receptors, scaffold and adapter proteins, cytoskeletal elements and signalling molecules. The stability of the PSD depends on a multiplicity of interactions linking individual components. At the same time the PSD retains a substantial degree of flexibility. The continuous exchange of synaptic molecules and the preferential addition or removal of certain components induce plastic changes in the synaptic structure. This property necessarily implies that interactors are in dynamic equilibrium and that not all synaptic binding sites are occupied simultaneously. This review discusses the molecular plasticity of inhibitory synapses in terms of the connectivity of their components. Whereas stable protein complexes are marked by stoichiometric relationships between subunits, the majority of synaptic interactions have fractional occupancy, which is here defined as the non-saturation of synaptic binding sites. Fractional occupancy can have several causes: reduced kinetic or thermodynamic stability of the interactions, an imbalance in the concentrations or limited spatio-temporal overlap of interacting proteins, negative cooperativity or mutually exclusive binding. The role of fractional occupancy in the regulation of synaptic structure and function is explored based on recent data about the connectivity of inhibitory receptors and scaffold proteins. I propose that the absolute quantification of interactors and their stoichiometry at identified synapses can provide new mechanistic insights into the dynamic properties of inhibitory PSDs at the molecular level. This article is part of the special issue entitled 'Mobility and trafficking of neuronal membrane proteins'.

中文翻译:

突触结合位点的部分占据和抑制性突触的分子可塑性。

抑制性突触的突触后密度(PSD)是一个复杂的分子组装体,可作为神经递质受体,支架和衔接蛋白,细胞骨架元件和信号分子相互作用的平台。PSD的稳定性取决于链接各个组件的多种交互作用。同时,PSD保留了很大程度的灵活性。突触分子的连续交换以及某些组分的优先添加或去除会引起突触结构的塑性变化。该性质必然意味着相互作用子处于动态平衡,并且并非所有突触结合位点都同时被占据。这篇评论讨论了抑制性突触的分子可塑性的组成部分之间的连通性。稳定的蛋白质复合物以亚基之间的化学计量关系为特征,而大多数突触相互作用具有部分占有率,在此将其定义为突触结合位点不饱和。分数占用可能有多种原因:相互作用的动力学或热力学稳定性降低,相互作用蛋白的浓度不平衡或时空重叠有限,负协同性或相互排斥结合。基于有关抑制性受体和支架蛋白的连接性的最新数据,探索了部分占据在突触结构和功能调节中的作用。我认为相互作用分子的绝对定量及其在确定的突触上的化学计量可以在分子水平上为抑制性PSD的动力学性质提供新的力学见解。本文是题为“神经元膜蛋白的移动性和运输”的特刊的一部分。
更新日期:2020-03-16
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