title: Quantitative proteomic profiling reveals novel region-specific markers in the adult mouse brain.
abstract: Despite major advances in neuroscience, a comprehensive understanding of the structural and functional components of the adult brain compartments remains to be fully elucidated at a quantitative molecular level. Indeed, over half of the soluble- and membrane-annotated proteins are currently unmapped within online digital brain atlases. In this study, two complementary approaches were used to assess the unique repertoire of proteins enriched within select regions of the adult mouse CNS, including the brain stem, cerebellum, and remaining brain hemispheres. Of the 1200 proteins visualized by 2D-DIGE, approximately 150 (including cytosolic and membrane proteins) were found to exhibit statistically significant changes in relative abundance thus representing putative region-specific brain markers. In addition to using a high-precision (18) O-labeling strategy for the quantitative LC-MS/MS mapping of membrane proteins isolated from myelin-enriched fractions, we have identified over 1000 proteins that have yet to be described in any other mammalian myelin proteome. A comparison of our myelin proteome was made to an existing transcriptome database containing mRNA abundance profiles during oligodendrocyte differentiation and has confirmed statistically significant abundance changes for ∼500 of these newly mapped proteins, thus revealing new roles in oligodendrocyte and myelin biology. These data offer a resource for the neuroscience community studying the molecular basis for specialized neuronal activities in the CNS and myelin-related disorders. The MS proteomics data associated with this manuscript have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000327 (http://proteomecentral.proteomexchange.org/dataset/PXD000327).
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia; Banting and Best Department of Medical Research, Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Dagley
authors.forename: Carl A
authors.initials: CA
authors.lastname: White
authors.forename: Yang
authors.initials: Y
authors.lastname: Liao
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Gordon K
authors.initials: GK
authors.lastname: Smyth
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Orian
authors.forename: Andrew
authors.initials: A
authors.lastname: Emili
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis*; D051379:Mice; D009186:Myelin Sheath / Q000737:chemistry; D010103:Oxygen Isotopes / Q000032:analysis; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D008565:Membrane Proteins; D010103:Oxygen Isotopes; D020543:Proteome
keywords: 18O-based stable isotope labeling; MS; Membrane proteins; Myelin interactome; Quantitative proteomics