Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5
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Abstract
Oligodendrocytes facilitate rapid impulse propagation along the axons they myelinate and support their long-term integrity. However, the functional relevance of many myelin proteins has remained unknown. Here, we find that expression of the tetraspan-transmembrane protein CMTM5 (chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) is highly enriched in oligodendrocytes and central nervous system (CNS) myelin. Genetic disruption of the Cmtm5 gene in oligodendrocytes of mice does not impair the development or ultrastructure of CNS myelin. However, oligodendroglial Cmtm5 deficiency causes an early-onset progressive axonopathy, which we also observe in global and tamoxifen-induced oligodendroglial Cmtm5 mutants. Presence of the Wld S mutation ameliorates the axonopathy, implying a Wallerian degeneration-like pathomechanism. These results indicate that CMTM5 is involved in the function of oligodendrocytes to maintain axonal integrity rather than myelin biogenesis.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Oligodendroglia metabolically support axons and contribute to neurodegeneration
Lee, Y., Morrison, B. M., Li, Y., Lengacher, S., Farah, M. H., Hoffman, P. N., Liu, Y., Tsingalia, A., Jin, L., Zhang, P.-W., et al. (2012) · Nature · doi:10.1038/nature11314 · Cited by 1,664 · cited 1× · see citing works
“Oligodendroglial support of axons involves several mechanisms, including supplying energy- rich substrates via monocarboxylate transporters (Fünfschilling et al., 2012; Lee et al., 2012; Philips et al., 2021; Trevisiol et al., 2020), allocating antioxidative proteins and other enzymes via extracellular vesicles (Chamb…”
BackgroundAbsolute Quantification of Proteins by LCMSE
Silva, J. C., Gorenstein, M. V., Li, G.-Z., Vissers, J. P. C., & Geromanos, S. J. (2006) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m500230-mcp200 · Cited by 1,529 · see citing works
Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity
Fünfschilling, U., Supplie, L. M., Mahad, D., Boretius, S., Saab, A. S., Edgar, J., Brinkmann, B. G., Kassmann, C. M., Tzvetanova, I. D., Möbius, W., et al. (2012) · Nature · doi:10.1038/nature11007 · Cited by 1,523 · see citing works
Self-citationDipy, a library for the analysis of diffusion MRI data
Garyfallidis, E., Brett, M., Amirbekian, B., Rokem, A., van der Walt, S., Descoteaux, M., Nimmo-Smith, I., & Contributors, D. (2014) · Frontiers in Neuroinformatics · doi:10.3389/fninf.2014.00008 · Cited by 1,371 · see citing works
Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism
Saab, A. S., Tzvetavona, I. D., Trevisiol, A., Baltan, S., Dibaj, P., Kusch, K., Möbius, W., Goetze, B., Jahn, H. M., Huang, W., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.05.016 · Cited by 590 · see citing works
Self-citationRapid Conduction and the Evolution of Giant Axons and Myelinated Fibers
Hartline, D. K., & Colman, D. R. (2007) · Current Biology · doi:10.1016/j.cub.2006.11.042 · Cited by 478 · see citing works
ROACH, A., TAKAHASHI, N., PRAVTCHEVA, D., RUDDLE, F., & HOOD, L. (1985) · Cell · doi:10.1016/s0092-8674(85)80110-0 · Cited by 336 · see citing works
A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration
Di Stefano, M., Nascimento-Ferreira, I., Orsomando, G., Mori, V, Gilley, J., Brown, R., Janeckova, L., Vargas, M. E., Worrell, L. A., Loreto, A., et al. (2015) · Cell Death & Differentiation · doi:10.1038/cdd.2014.164 · Cited by 246 · see citing works
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- Authors
- Buscham, T. J., Eichel-Vogel, M. A., Steyer, A. M., Jahn, O., Strenzke, N., Dardawal, R., Memhave, T. R., Siems, S. B., Müller, C., Meschkat, M., Sun, T., Ruhwedel, T., Möbius, W., Krämer-Albers, E.-M., Boretius, S., Nave, K.-A., & Werner, H. B.
- Affiliations
- Max Planck Institute of Experimental Medicine (DE)
- Department of Neurogenetics, Max Planck Institute of Experimental Medicine
- Universitätsmedizin Göttingen (DE)
- German Primate Center (DE)
- Johannes Gutenberg University Mainz (DE)
- Institute of Developmental Biology and Neurobiology, Johannes Gutenberg University
- Corresponding author
- Werner, Hauke B
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-03-11
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC8916772
- OpenAlex
- W4220763990
- Cited by
- 18
- References
- 10
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 6 · 2023: 6 · 2022: 2
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (WE 2720/2-2, WE 2720/4-1, WE 2720/5-1)
- European Research Council (Advanced Grant MyeliNano)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- oligodendrocytes, axonopathy, myelin proteins, Wallerian degeneration, axonal integrity, myelin biogenesis, central nervous system myelin
- MeSH terms
- Animals, Axons, Central Nervous System, Myelin Proteins, Myelin Sheath, Oligodendroglia, Mice
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