Spatially-Resolved Top-down Proteomics Bridged to MALDI MS Imaging Reveals the Molecular Physiome of Brain Regions

Mol Cell Proteomics. 2018 Feb;17(2):357-372. doi: 10.1074/mcp.M116.065755. Epub 2017 Nov 9.

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 α-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Male
  • Proteome*
  • Proteomics
  • Rats, Wistar
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Proteome

Grants and funding