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Abstract

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.