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脑发育过程中的亚细胞蛋白质组动态。

Dynamics of subcellular proteomes during brain development.

机构信息

The Scripps Research Institute, La Jolla, California 92037, United States.

出版信息

J Proteome Res. 2012 Apr 6;11(4):2467-79. doi: 10.1021/pr201176v. Epub 2012 Mar 26.

Abstract

Many neurological disorders are caused by perturbations during brain development, but these perturbations cannot be readily identified until there is comprehensive description of the development process. In this study, we performed mass spectrometry analysis of the synaptosomal and mitochondrial fractions from three rat brain regions at four postnatal time points. To quantitate our analysis, we employed (15)N labeled rat brains using a technique called SILAM (stable isotope labeling in mammals). We quantified 167429 peptides and identified over 5000 statistically significant changes during development including known disease-associated proteins. Global analysis revealed distinct trends between the synaptic and nonsynaptic mitochondrial proteomes and common protein networks between regions each consisting of a unique array of expression patterns. Finally, we identified novel regulators of neurodevelopment that possess the identical temporal pattern of known regulators of neurodevelopment. Overall, this study is the most comprehensive quantitative analysis of the developing brain proteome to date, providing an important resource for neurobiologists.

摘要

许多神经紊乱是由大脑发育过程中的干扰引起的,但在对发育过程进行全面描述之前,这些干扰无法轻易识别。在这项研究中,我们对四个出生后时间点的三个大鼠脑区的突触体和线粒体部分进行了质谱分析。为了定量我们的分析,我们使用一种称为 SILAM(哺乳动物中稳定同位素标记)的技术对(15)N 标记的大鼠脑进行了标记。我们定量了 167429 个肽,并在发育过程中发现了 5000 多个具有统计学意义的变化,包括已知与疾病相关的蛋白质。全局分析显示突触体和非突触体线粒体蛋白质组之间存在明显的趋势,并且每个区域之间都存在共同的蛋白质网络,这些网络由独特的表达模式组成。最后,我们确定了一些新的神经发育调节剂,它们具有与已知神经发育调节剂相同的时间模式。总的来说,这是迄今为止对发育中大脑蛋白质组进行的最全面的定量分析,为神经生物学家提供了一个重要的资源。

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