Dynamics of Subcellular Proteomes During Brain Development

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 15N 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.众多神经系统疾病由脑发育过程中的扰动所引发，但此类扰动往往难以直接识别，唯有对脑发育进程形成全面刻画后方可实现精准辨识。本研究针对三个大鼠脑区在四个出生后时间点的突触体与线粒体组分开展了质谱分析。为完成定量分析，我们采用了名为SILAM（stable isotope labeling in mammals）的技术，使用经15N标记的大鼠脑组织样本。本研究共定量到167429条肽段，鉴定出发育过程中超过5000处具有统计学意义的表达变化，其中包含已被报道的疾病相关蛋白。整体分析揭示了突触线粒体与非突触线粒体蛋白质组间的显著表达差异趋势，同时发现不同脑区间存在共通的蛋白质调控网络，且各脑区均拥有独特的表达谱特征。最后，本研究鉴定出一批全新的神经发育调控因子，它们与已知神经发育调控因子具备完全一致的时序表达模式。总体而言，本研究是目前为止对发育中脑蛋白质组最为全面的定量分析，可为神经生物学家提供重要的研究资源。