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Systematic approaches to central nervous system myelin

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Abstract

Rapid signal propagation along vertebrate axons is facilitated by their insulation with myelin, a plasma membrane specialization of glial cells. The recent application of ‘omics’ approaches to the myelinating cells of the central nervous system, oligodendrocytes, revealed their mRNA signatures, enhanced our understanding of how myelination is regulated, and established that the protein composition of myelin is much more complex than previously thought. This review provides a meta-analysis of the >1,200 proteins thus far identified by mass spectrometry in biochemically purified central nervous system myelin. Contaminating proteins are surprisingly infrequent according to bioinformatic prediction of subcellular localization and comparison with the transcriptional profile of oligodendrocytes. The integration of datasets also allowed the subcategorization of the myelin proteome into functional groups comprising genes that are coregulated during oligodendroglial differentiation. An unexpectedly large number of myelin-related genes cause—when mutated in humans—hereditary diseases affecting the physiology of the white matter. Systematic approaches to oligodendrocytes and myelin thus provide valuable resources for the molecular dissection of developmental myelination, glia–axonal interactions, leukodystrophies, and demyelinating diseases.

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Abbreviations

CNS:

Central nervous system

Ig-CAM:

Immunoglobulin-like cell adhesion molecule

MBP:

Myelin basic protein

mOL:

Myelinating oligodendrocyte

MS:

Mass spectrometry/mass spectrometric

OPC:

Oligodendrocyte precursor cell

P0:

Myelin protein zero

PLP:

Proteolipid protein

PNS:

Peripheral nervous system

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Acknowledgments

We thank W. Möbius for providing the electron micrograph in Fig. 1, J. M. Edgar for critical reading of the manuscript, C. M. Kassmann for discussion, and K.-A. Nave for continuous support. ST is supported by the Deutsche Forschungsgemeinschaft (SFB 490 Z3) and the Forschungszentrum Immunologie (FZI) at the University of Mainz, and HBW is supported by the BMBF (DLR-Leukonet) and the European Commission (FP7-LeukoTreat).

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Authors and Affiliations

  1. Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075, Göttingen, Germany

    Patricia de Monasterio-Schrader, Sven P. Wichert, Julia Patzig & Hauke B. Werner

  2. Proteomics Group, Max Planck Institute of Experimental Medicine, Göttingen, Germany

    Olaf Jahn

  3. DFG Research Center for Molecular Physiology of the Brain, Göttingen, Germany

    Olaf Jahn

  4. Institute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

    Stefan Tenzer

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  1. Patricia de Monasterio-Schrader
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  2. Olaf Jahn
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  3. Stefan Tenzer
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  4. Sven P. Wichert
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  5. Julia Patzig
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  6. Hauke B. Werner
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Correspondence to Hauke B. Werner.

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18_2012_958_MOESM1_ESM.xls

Supplementary material 1 Supplemental Table S1. Compendium of proteins identified by mass spectrometry in CNS myelin. Out of the 1,280 proteins listed, 1,261 proteins could be assigned to a unique gene identifier, of which 1,249 could be correlated with the oligodendroglial transcriptome as established by [9] (last column). The proteins are classified into three groups: known myelin proteins, proteins identified by MS in myelin, and proteins presumably derived from mitochondria that contaminate the myelin-enriched fraction. Identification of a protein in one of the 11 available proteomic datasets (see main text for references) is indicated by “1″. Potential mitochondrial localization was classified by prior knowledge (MitoCarta) and prediction of subcellular localization according to three algorithms (TargetP, Cello, Wolfpsort). The number of transmembrane domains was predicted by three algorithms (TMpred, TMHMM, Phobius). If available, correlation with a large-scale in situ-hybridization dataset (‘Allen Brain Atlas‘) is provided (OL oligodendrocyte; AS astrocyte; NE, neuron) according to supplemental table 11 in [137](XLS 606 kb)

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de Monasterio-Schrader, P., Jahn, O., Tenzer, S. et al. Systematic approaches to central nervous system myelin. Cell. Mol. Life Sci. 69, 2879–2894 (2012). https://doi.org/10.1007/s00018-012-0958-9

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