Dynamics of subcellular proteomes during brain development

Daniel B. McClatchy, Lujian Liao, Ji Hyoung Lee, Sung Kyu Park, John R. Yates

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 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.

Original languageEnglish
Pages (from-to)2467-2479
Number of pages13
JournalJournal of Proteome Research
Volume11
Issue number4
DOIs
StatePublished - 6 Apr 2012
Externally publishedYes

Keywords

  • MudPIT
  • SILAM
  • brain development
  • metabolic labeling
  • quantitation

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