Spatially-Resolved Top-down Proteomics Bridged to MALDI MS Imaging Reveals the Molecular Physiome of Brain Regions
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American Society for Biochemistry and Molecular Biology Inc.
Abstract
Tissue spatially-resolved proteomics was performed on 3 brain regions, leading to the characterization of 123 reference proteins. Moreover, 8 alternative proteins from alternative open reading frames (AltORF) were identified. Some proteins display specific post-translational modification profiles or truncation linked to the brain regions and their functions. Systems biology analysis performed on the proteome identified in each region allowed to associate sub-networks with the functional physiology of each brain region. Back correlation of the proteins identified by spatially-resolved proteomics at a given tissue localization with the MALDI MS imaging data, was then performed. As an example, mapping of the distribution of the matrix metallopeptidase 3-cleaved C-terminal fragment of -synuclein (aa 95–140) identified its specific distribution along the hippocampal dentate gyrus. Taken together, we established the molecular physiome of 3 rat brain regions through reference and hidden proteome characterization. Molecular & Cellular Proteomics 17: 10.1074/mcp.M116.065755, 357–372, 2018.
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Animals, Brain, Male, Proteome, Proteomics, Rats, wistar, Spectrometry, mass, matrix-assisted laser desorption-ionization, Alpha synuclein, Apex protein, Beta synuclein, Calmodulin, Chromogranin b, Cytochrome c oxidase, Gamma synuclein, Hematological and neurological expressed 1, Lipid, Myelin basic protein, Neuromodulin, Oxidoreductase, Parathymosin, Pep 19 protein, Proenkephalin, Protein, Secretogranin ii, Somatostatin, Stromelysin, Synaptosomal associated protein 25, Thymosin beta10, Thymosin beta4, Ubiquitin, Unclassified drug, 3' untranslated region, 5' untranslated region, Animal tissue, Article, Brain function, Brain region, Brain tissue, Cell damage, Cell proliferation, Controlled study, Corpus callosum, Enzyme activity, Hippocampus, Matrix-assisted laser desorption-ionization mass spectrometry, Medulla oblongata, Nervous system development, Nonhuman, Oxidative stress, Priority journal, Protein analysis, Rat, Synaptogenesis, Animal, Metabolism, Wistar rat