|Myelin proteome analysis|
Central nervous system
|Dr. Hauke Werner
Department of Neurogenetics
Peripheral nervous system
|Dr. Olaf Jahn
|References||We have established a method to systematically analyze the protein composition of central nervous system (CNS) myelin, making use of 2-dimensional gel-based separation and an automated platform for mass spectrometric protein identification. These and complementary gel-free approaches resulted in a catalogue of myelin-associated proteins providing a resource for a better understanding of myelin biogenesis, function, and disease (Jahn et al., 2009; Werner & Jahn, 2010). It is also a prerequisite for differential myelin proteome analysis.|
|Such a differential approach has first been applied to mice lacking the expression of PLP/DM20 in oligodendrocytes. PLPnull mice provide a genuine model for spastic paraplegia (SPG-2), a mild variant of the leukodystrophy Pelizaeus-Merzbacher Disease. Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which has been difficult to attribute to the absence of a single myelin protein. Differential proteome analysis prior to the onset of disease has identified secondary molecular changes in PLPnull myelin that may contribute to the loss of PLP/DM20-dependent neuroprotection and provide more insight into glia-axonal interactions in this disease model (Werner et al., 2007).|
|Recently, we have established a meta-analysis of the >1200 proteins thus far identified by mass spectrometry in CNS myelin (de Monasterio-Schrader et al., 2012).|
|Click here to download the CNS dataset (supplement to de Monasterio-Schrader et al., 2012). (File generated using Microsoft Excel [Version: Office 2003]; 604kB).|
|Peripheral myelin differs from central myelin regarding the ontogenic origin of the myelinating glial cell, ultrastructure, and molecular composition. We have established the first proteomic compendium of the proteins associated with PNS myelin using various state-of-the-art techniques. It was possible to integrate the dataset with other systematic approaches, including mRNA-abundance profiles in peripheral nerves, prediction of transmembrane domains and subcellular localization, functional annotations, and association of the corresponding human genes with neuropathy disease loci. Our results illustrate how the integration of unbiased proteome, transcriptome, and genome data can contribute to a molecular dissection of the biogenesis, cell biology, metabolism, and pathology of myelin.|
|Click here to download the PNS dataset (supplement to Patzig et al., 2011). (File generated using Microsoft Excel [Version: Office 2003]; 192kB).|
|We have also analyzed alterations in the protein composition of peripheral myelin in a neuropathy disease model. Mice lacking the expression of prion protein (Prnp0/0) constitute a model of chronic polyneuropathy involving demyelination. In this model, prion protein (PrPC) expressed in neurons is an axonal signal for the prevention of demyelination. By differential proteome analysis we have identified a particular secondary molecular change in Prnp0/0 myelin that may contribute to the demyelination in this neuropathy model (Patzig et al. 2011).|
|We are closely working together with -> Dr. Stefan Tenzer at the Institute for Immunology, University of Mainz, Germany.|
|Detailed information in (references):|
|to top of page||Jahn O, Tenzer S, Bartsch N, Patzig J, Werner HB. (2013) Myelin proteome analysis: Methods and implications for the myelin cytoskeleton. In: Dermietzel R, (ed.); The cytoskeleton: Imaging, isolation, and interaction. Neuromethods, vol. 79, 335-353 (Springer).
de Monasterio-Schrader P, Jahn O, Tenzer S, Wichert SP, Patzig J, Werner HB (2012) Systematic approaches to central nervous system myelin. Cellular and Molecular Life Sciences 69:2879-94. The final publication is available at -> www.springerlink.com.
Click here to download an author-generated PDF-version of the article (1,78MB).
Patzig J, Jahn O, Tenzer S, Wichert SP, de Monasterio-Schrader P, Rosfa S, Kuharev J, Yan K, Bormuth I, Bremer J, Aguzzi A, Orfaniotou F, Hesse D, Schwab MH, Möbius W, Nave KA, Werner HB (2011) Quantitative and integrative proteome analysis of peripheral nerve myelin identifies novel myelin proteins and candidate neuropathy loci. Journal of Neuroscience 31(45):16369-16386.
Werner HB, Jahn O (2010) Myelin matters: Proteomic insights into white matter disorders. Expert Review of Proteomics 7:159-64.
Jahn O, Tenzer S, Werner HB (2009) Myelin proteomics: Molecular anatomy of an insulating sheath. Molecular Neurobiology 40:55-72.
Werner HB, Kuhlmann K, Shen S, Uecker M, Schardt A, Dimova K, Orfaniotou F, Dhaunchak A, Brinkmann BG, Möbius W, Guarente L, Casaccia-Bonnefil P, Jahn O, Nave KA (2007) Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. Journal of Neuroscience 27:7717-30.