Systematic approaches to central nervous system myelin
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Cellular and Molecular Life Sciences
REVIEW
Systematic approaches to central nervous system myelin Patricia de Monasterio-Schrader • Olaf Jahn • Stefan Tenzer • Sven P. Wichert • Julia Patzig Hauke B. Werner
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Received: 9 February 2012 / Accepted: 5 March 2012 / Published online: 23 March 2012 Ó Springer Basel AG 2012
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 Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-0958-9) contains supplementary material, which is available to authorized users. P. de Monasterio-Schrader S. P. Wichert J. Patzig H. B. Werner (&) Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Str. 3, 37075 Go¨ttingen, Germany e-mail: [email protected] O. Jahn Proteomics Group, Max Planck Institute of Experimental Medicine, Go¨ttingen, Germany O. Jahn DFG Research Center for Molecular Physiology of the Brain, Go¨ttingen, Germany S. Tenzer Institute of Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
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. Keywords Oligodendrocyte Myelin Differentiation Proteome Transcriptome Leukodystrophy Schizophrenia Multiple sclerosis 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
Introduction Fast signal propagation along vertebrate axons requires the restriction of action potentials to short axonal segments, termed the nodes of Ranvier. This is achieved by the insulation of the long segments between the nodes (‘internodes’) with a
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