Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5

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 WldS 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.

Publication
eLife Sciences Publications, Ltd
Rakshit Dadarwal
Rakshit Dadarwal
Postdoctoral Researcher

My research focuses on the acquisition and processing of multi-contrast magnetic resonance imaging (MRI) data. I am particularly interested in imaging myelin and iron in the central nervous system and studying healthy aging in non-human primates using Diffusion-weighted Imaging (DWI), Quantitative Susceptibility Mapping (QSM), Magnetization Transfer Imaging, and T1 and T2-relaxometry.

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