CMTM6 expressed on the adaxonal Schwann cell surface restricts axonal diameters in peripheral nerves

Maria A. Eichel, Vasiliki-Ilya Gargareta, Elisa D’Este, Robert Fledrich, Theresa Kungl, Tobias J. Buscham, Katja A. Lüders, Cristina Miracle, Ramona B. Jung, Ute Distler, Kathrin Kusch, Wiebke Möbius, Swen Hülsmann, Stefan Tenzer, Klaus-Armin Nave and Hauke B. Werner ()
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Maria A. Eichel: Max Planck Institute of Experimental Medicine
Vasiliki-Ilya Gargareta: Max Planck Institute of Experimental Medicine
Elisa D’Este: Max Planck Institute for Biophysical Chemistry
Robert Fledrich: Max Planck Institute of Experimental Medicine
Theresa Kungl: Max Planck Institute of Experimental Medicine
Tobias J. Buscham: Max Planck Institute of Experimental Medicine
Katja A. Lüders: Max Planck Institute of Experimental Medicine
Cristina Miracle: Max Planck Institute of Experimental Medicine
Ramona B. Jung: Max Planck Institute of Experimental Medicine
Ute Distler: Johannes Gutenberg University
Kathrin Kusch: Max Planck Institute of Experimental Medicine
Wiebke Möbius: Max Planck Institute of Experimental Medicine
Swen Hülsmann: University Medical Center
Stefan Tenzer: Johannes Gutenberg University
Klaus-Armin Nave: Max Planck Institute of Experimental Medicine
Hauke B. Werner: Max Planck Institute of Experimental Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract The velocity of nerve conduction is moderately enhanced by larger axonal diameters and potently sped up by myelination of axons. Myelination thus allows rapid impulse propagation with reduced axonal diameters; however, no myelin-dependent mechanism has been reported that restricts radial growth of axons. By label-free proteomics, STED-microscopy and cryo-immuno electron-microscopy we here identify CMTM6 (chemokine-like factor-like MARVEL-transmembrane domain-containing family member-6) as a myelin protein specifically localized to the Schwann cell membrane exposed to the axon. We find that disruption of Cmtm6-expression in Schwann cells causes a substantial increase of axonal diameters but does not impair myelin biogenesis, radial sorting or integrity of axons. Increased axonal diameters correlate with accelerated sensory nerve conduction and sensory responses and perturbed motor performance. These data show that Schwann cells utilize CMTM6 to restrict the radial growth of axons, which optimizes nerve function.

Date: 2020
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DOI: 10.1038/s41467-020-18172-7

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