The CNS Myelin Proteome: Deep Profile and Persistence After Post-mortem Delay

• Main Authors: Olaf Jahn, Sophie B. Siems, Kathrin Kusch, Dörte Hesse, Ramona B. Jung, Thomas Liepold, Marina Uecker, Ting Sun, Hauke B. Werner
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-08-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: oligodendrocyte; myelin proteome; central nervous system (CNS); demyelination; post-mortem delay; autopsy
• Online Access: https://www.frontiersin.org/article/10.3389/fncel.2020.00239/full

Myelin membranes are dominated by lipids while the complexity of their protein composition has long been considered to be low. However, numerous additional myelin proteins have been identified since. Here we revisit the proteome of myelin biochemically purified from the brains of healthy c56Bl/6N-mice utilizing complementary proteomic approaches for deep qualitative and quantitative coverage. By gel-free, label-free mass spectrometry, the most abundant myelin proteins PLP, MBP, CNP, and MOG constitute 38, 30, 5, and 1% of the total myelin protein, respectively. The relative abundance of myelin proteins displays a dynamic range of over four orders of magnitude, implying that PLP and MBP have overshadowed less abundant myelin constituents in initial gel-based approaches. By comparisons with published datasets we evaluate to which degree the CNS myelin proteome correlates with the mRNA and protein abundance profiles of myelin and oligodendrocytes. Notably, the myelin proteome displays only minor changes if assessed after a post-mortem delay of 6 h. These data provide the most comprehensive proteome resource of CNS myelin so far and a basis for addressing proteomic heterogeneity of myelin in mouse models and human patients with white matter disorders.