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

• Published in: Nature communications Vol. 11; no. 1; pp. 4514 - 12
• Main Authors: Eichel, Maria A., Gargareta, Vasiliki-Ilya, D’Este, Elisa, Fledrich, Robert, Kungl, Theresa, Buscham, Tobias J., Lüders, Katja A., Miracle, Cristina, Jung, Ramona B., Distler, Ute, Kusch, Kathrin, Möbius, Wiebke, Hülsmann, Swen, Tenzer, Stefan, Nave, Klaus-Armin, Werner, Hauke B.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-09-2020; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/28; 45/41; 631/378/1959; 631/378/2596/3921; 631/378/87; 64/60; 82/51; Animals; Axonogenesis; Axons; Axons - metabolism; Axons - ultrastructure; Cell membranes; Cell surface; Chemokines; Cryoelectron Microscopy; Humanities and Social Sciences; Male; MARVEL Domain-Containing Proteins - metabolism; Mice; Mice, Knockout; Microscopy; Motor task performance; multidisciplinary; Myelin; Myelin Proteins - metabolism; Myelin Sheath - metabolism; Myelin Sheath - ultrastructure; Myelination; Nerve conduction; Neural Conduction; Peripheral nerves; Peripheral Nerves - cytology; Peripheral Nerves - metabolism; Peripheral Nerves - ultrastructure; Proteomics; Schwann cells; Schwann Cells - cytology; Schwann Cells - metabolism; Schwann Cells - ultrastructure; Science; Science (multidisciplinary); Sensory neurons; Sensory Receptor Cells - cytology; Sensory Receptor Cells - metabolism; Sensory Receptor Cells - ultrastructure
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-18172-7

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.
Myelinating cells differentially myelinate axons of different diameters, however whether they can also restrict radial axonal growth remained unclear. Here, the authors show that CMTM6 in Schwann cells restricts axon diameters, affecting sensory nerve conduction and behavioral performance.