Abstract:
The postsynaptic density (PSD) is a collection of specialized proteins assembled beneath the postsynaptic membrane of dendritic spines. The PSD proteome comprises ~1000 proteins, including neurotransmitter receptors, scaffolding proteins and signalling enzymes. Many of these proteins have essential roles in synaptic function and plasticity. During brain development, changes are observed in synapse density and in the stability and shape of spines, reflecting the underlying molecular maturation of synapses. Synaptic protein composition changes in terms of protein abundance and the assembly of protein complexes, supercomplexes and the physical organization of the PSD. Here, we summarize the developmental alterations of postsynaptic protein composition during synapse maturation. We describe major PSD proteins involved in postsynaptic signalling that regulates synaptic plasticity and discuss the effect of altered expression of these proteins during development. We consider the abnormality of synaptic profiles and synaptic protein composition in the brain in neurodevelopmental disorders such as autism spectrum disorders. We also explain differences in synapse development between rodents and primates in terms of synaptic profiles and protein composition. Finally, we introduce recent findings related to synaptic diversity and nanoarchitecture and discuss their impact on future research. Synaptic protein composition can be considered a major determinant and marker of synapse maturation in normality and disease.
摘要:
突触后密度(PSD)是在树突棘的突触后膜下组装的特化蛋白质的集合。PSD蛋白质组包含约1000种蛋白质,包括神经递质受体,支架蛋白和信号酶。这些蛋白质中的许多在突触功能和可塑性中具有重要作用。在大脑发育过程中,观察到突触密度和脊柱的稳定性和形状的变化,反映了突触的潜在分子成熟。突触蛋白组成在蛋白质丰度和蛋白质复合物组装方面的变化,超复合物和PSD的物理组织。这里,我们总结了突触成熟过程中突触后蛋白组成的发育变化。我们描述了参与调节突触可塑性的突触后信号传导的主要PSD蛋白,并讨论了这些蛋白在发育过程中表达改变的影响。我们考虑了神经发育障碍如自闭症谱系障碍中大脑中突触谱和突触蛋白组成的异常。我们还解释了啮齿动物和灵长类动物在突触谱和蛋白质组成方面的突触发育差异。最后,我们介绍了与突触多样性和纳米结构相关的最新发现,并讨论了它们对未来研究的影响。突触蛋白组成可以被认为是正常状态和疾病中突触成熟的主要决定因素和标志物。