Regional Diversity and Developmental Dynamics of the AMPA-Receptor Proteome in the Mammalian Brain
Regional Diversity and Developmental Dynamics of the AMPA-Receptor Proteome in the Mammalian Brain
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DOI：
10.1016/j.neuron.2014.08.044
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发表时间：
2014-10-01
期刊：
影响因子：
16.2
通讯作者：
Schulte, Uwe
中科院分区：
文献类型：
--
作者：
Schwenk, Jochen;Baehrens, David;Schulte, Uwe
哺乳动物脑中的天然AMPA受体（AMPAR）是大分子复合物，其功能特征在不同脑区域中变化，并且在出生后发育期间或响应于神经元活动而变化。AMPAR的结构和功能特性由它们的蛋白质组决定，蛋白质组是它们的蛋白质构建块的集合。在这里，我们使用高分辨率定量质谱分析AMPAR的亲和力，从不同的大脑区域，选定的神经元集，并在出生后发育的不同阶段的整个大脑分离的整个池。这些分析表明，AMPAR蛋白质组在空间和时间上都是动态的：AMPAR在其结构和构建其核心和外围的成分中表现出深刻的区域特异性。同样，AMPAR在出生后的发育过程中交换了许多构建模块。这些结果提供了一个独特的资源和详细的上下文数据集分析本地AMPAR复合物及其在兴奋性神经传递中的作用。
Native AMPA receptors (AMPARs) in the mammalian brain are macromolecular complexes whose functional characteristics vary across the different brain regions and change during postnatal development or in response to neuronal activity. The structural and functional properties of the AMPARs are determined by their proteome, the ensemble of their protein building blocks. Here we use high-resolution quantitative mass spectrometry to analyze the entire pool of AMPARs affinity-isolated from distinct brain regions, selected sets of neurons, and whole brains at distinct stages of postnatal development. These analyses show that the AMPAR proteome is dynamic in both space and time: AMPARs exhibit profound region specificity in their architecture and the constituents building their core and periphery. Likewise, AMPARs exchange many of their building blocks during postnatal development. These results provide a unique resource and detailed contextual data sets for the analysis of native AMPAR complexes and their role in excitatory neurotransmission.