Progressive axonopathy when oligodendrocytes lack the myelin protein CMTM5.
Tobias J BuschamMaria A Eichel-VogelAnna M SteyerOlaf JahnNicola StrenzkeRakshit DardawalTor R MemhaveSophie B SiemsChristina MüllerMartin MeschkatTing SunTorben RuhwedelWiebke MöbiusEva-Maria Krämer-AlbersSusann BoretiusKlaus-Armin NaveHauke B WernerPublished in: eLife (2022)
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.
Keyphrases
- early onset
- white matter
- multiple sclerosis
- binding protein
- protein protein
- amino acid
- blood brain barrier
- poor prognosis
- genome wide
- copy number
- spinal cord injury
- type diabetes
- gene expression
- metabolic syndrome
- mouse model
- adipose tissue
- cerebrospinal fluid
- breast cancer cells
- quantum dots
- positive breast cancer
- skeletal muscle
- optical coherence tomography
- high fat diet induced
- loop mediated isothermal amplification