CMTM5 - a novel CNS myelin protein involved in preserving axonal integrity

Myelination of axons in the nervous system facilitates rapid, saltatory signal propagation, accelerating nerve conduction speed manyfold. Additionally, myelinating glia support the long-term integrity of axons they enwrap. However, the relevance of many myelin proteins in these processes has remained elusive. In this study we identify CMTM5 (Chemokine-like factor-like MARVEL-transmembrane domain containing protein 5) as a low abundant but highly specific constituent of CNS myelin. We find that genetic disruption of the Cmtm5-gene in myelinating glial cells in mice does not alter myelin development or ultrastructure. However, deletion of Cmtm5 in oligodendrocytes causes a progressive axonopathy in the CNS that is ameliorated by presence of the Wlds mutation, suggesting a Wallerian like mechanism of axon degeneration. Ablation of Cmtm5 in myelinating Schwann cells of the PNS leads to a reduction in axonal diameters without evident axonal pathology, suggesting that CMTM5 serves different roles in the CNS and the PNS, respectively. Our results indicate that CMTM5 is not crucial for myelin biogenesis, structure, or composition but contributes to the functions of oligodendrocytes in maintaining axonal integrity in the CNS.2022-05-0