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Peer-reviewedCC BYNature Neuroscience

An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes

  • Katie J. Chapple1
  • Tabitha R. F. Green1
  • Kristen H. Schuster2
  • Sarah Wirth1
  • Yi-Hsin Chen1
  • Ulrike C. Gerwig3
  • Marie Louise Aicher3
  • Yeonsu Kim3
  • Lina Komarek3,1
  • Angus M. Brown4
  • Colin L. Crawford1
  • Rebecca Sherrard Smith1
14 more authors
  • Young Seok Lee5
  • Lauren Elaine Black1
  • Luis Pardo1
  • Rebecca E. McHugh1
  • Celia M. Kassmann3
  • Wiebke Möbius3,6
  • Hauke B. Werner3,7
  • Ilan Davis1,5
  • Matthias Kneussel8
  • Ethan G. Hughes2
  • Euan R. Brown9
  • Sandra Goebbels3
  • Klaus‐Armin Nave10,11
  • Julia M. Edgar12,13
13 affiliations
  1. 1School of Infection & Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  2. 2Department of Cell and Developmental Biology, University of Colorado, School of Medicine, Aurora, CO, USA
  3. 3Dept of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany
  4. 4School of Life Sciences, University of Nottingham, Nottingham, UK
  5. 5School of Molecular Biosciences, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  6. 6Electron Microscopy-City Campus, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
  7. 7Faculty of Biology and Psychology, University of Göttingen, Göttingen, Germany
  8. 8Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  9. 9School of Engineering and Physical Sciences, Institute of Biological Chemistry, Biophysics and Bioengineering, Heriot Watt University, Edinburgh, UK
  10. 10Department of Neuropathology, Charité Universitätsmedizin, Berlin, Germany. [email protected]
  11. 11Dept of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany. [email protected]
  12. 12Dept of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, City Campus, Göttingen, Germany. [email protected]
  13. 13School of Infection & Immunity, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. [email protected]
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Abstract

Myelin sheaths comprise compacted layers of membrane wrapped around axons. Each sheath, if 'unwrapped', has a cytoplasm-filled space at its perimeter. Transmission electron microscopy reveals that this space contains microtubules and organelles; however, whether these are developmental remnants or serve a specific function remains unknown. Live imaging of myelinating oligodendrocytes in mice showed microtubule-dependent organelle transport within myelin sheath cytoplasmic spaces. Further, movement of myelin-located peroxisomes was modulated by neuronal electrical activity, in vitro and in vivo. Loss of oligodendroglial KIF21B and/or CNP in vivo led to the apparent stasis of myelin organelles and secondary axon pathology. We, thus, propose the acronym TRAM (transport route across myelin), defining the continuous cytoplasmic network in oligodendrocytes and myelin. This system, comprising the inner and outer tongues and paranodal loops, spans compact myelin and enables transport of metabolites and organelles between the oligodendrocyte soma and the periaxonal space.

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Cite

BibTeXRIS
BibTeX
@article{chapple2026activitymodulated,
  title = {{An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes}},
  author = {Katie J. Chapple and Tabitha R. F. Green and Kristen H. Schuster and Sarah Wirth and Yi-Hsin Chen and Ulrike C. Gerwig and Marie Louise Aicher and Yeonsu Kim and Lina Komarek and Angus M. Brown and Colin L. Crawford and Rebecca Sherrard Smith and Young Seok Lee and Lauren Elaine Black and Luis Pardo and Rebecca E. McHugh and Celia M. Kassmann and Wiebke Möbius and Hauke B. Werner and Ilan Davis and Matthias Kneussel and Ethan G. Hughes and Euan R. Brown and Sandra Goebbels and Klaus‐Armin Nave and Julia M. Edgar},
  journal = {Nature Neuroscience},
  year = {2026},
  month = jul,
  doi = {10.1038/s41593-026-02383-0},
  url = {https://doi.org/10.1038/s41593-026-02383-0},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - An activity-modulated transport route across myelin (TRAM) for motor-driven organelle transfer in oligodendrocytes
AU  - Katie J. Chapple
AU  - Tabitha R. F. Green
AU  - Kristen H. Schuster
AU  - Sarah Wirth
AU  - Yi-Hsin Chen
AU  - Ulrike C. Gerwig
AU  - Marie Louise Aicher
AU  - Yeonsu Kim
AU  - Lina Komarek
AU  - Angus M. Brown
AU  - Colin L. Crawford
AU  - Rebecca Sherrard Smith
AU  - Young Seok Lee
AU  - Lauren Elaine Black
AU  - Luis Pardo
AU  - Rebecca E. McHugh
AU  - Celia M. Kassmann
AU  - Wiebke Möbius
AU  - Hauke B. Werner
AU  - Ilan Davis
AU  - Matthias Kneussel
AU  - Ethan G. Hughes
AU  - Euan R. Brown
AU  - Sandra Goebbels
AU  - Klaus‐Armin Nave
AU  - Julia M. Edgar
PY  - 2026
DA  - 2026/07/31
JO  - Nature Neuroscience
DO  - 10.1038/s41593-026-02383-0
UR  - https://doi.org/10.1038/s41593-026-02383-0
AB  - Myelin sheaths comprise compacted layers of membrane wrapped around axons. Each sheath, if 'unwrapped', has a cytoplasm-filled space at its perimeter. Transmission electron microscopy reveals that this space contains microtubules and organelles; however, whether these are developmental remnants or serve a specific function remains unknown. Live imaging of myelinating oligodendrocytes in mice showed microtubule-dependent organelle transport within myelin sheath cytoplasmic spaces. Further, movement of myelin-located peroxisomes was modulated by neuronal electrical activity, in vitro and in vivo. Loss of oligodendroglial KIF21B and/or CNP in vivo led to the apparent stasis of myelin organelles and secondary axon pathology. We, thus, propose the acronym TRAM (transport route across myelin), defining the continuous cytoplasmic network in oligodendrocytes and myelin. This system, comprising the inner and outer tongues and paranodal loops, spans compact myelin and enables transport of metabolites and organelles between the oligodendrocyte soma and the periaxonal space.
SN  - 1097-6256
SN  - 1546-1726
ER  -