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Cell. 2014 Jan 16;156(1-2):277-90. doi: 10.1016/j.cell.2013.11.044.

Myelin membrane wrapping of CNS axons by PI(3,4,5)P3-dependent polarized growth at the inner tongue.

Author information

1
Max Planck Institute of Experimental Medicine, Cellular Neuroscience, Hermann-Rein-Strasse, 3, 37075 Göttingen, Germany; Department of Neurology, University of Göttingen, Robert-Koch-Strasse, 40, 37075 Göttingen, Germany.
2
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse, 3, 37075 Göttingen, Germany; Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
3
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK; MS Society Centre for Translational Research, University of Edinburgh, Edinburgh EH16 4SB, UK; Euan Mac Donald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK; MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, UK.
4
FEI Company, Achtseweg Noord 5, 5651 GG Eindhoven, The Netherlands.
5
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse, 3, 37075 Göttingen, Germany.
6
Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland; Division of Clinical Pathology, Geneva University Hospital, 1211 Geneva, Switzerland; Department of Neuropathology, University of Göttingen, 37075 Göttingen, Germany.
7
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, UK; MS Society Centre for Translational Research, University of Edinburgh, Edinburgh EH16 4SB, UK; Euan Mac Donald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.
8
Max Planck Institute of Experimental Medicine, Cellular Neuroscience, Hermann-Rein-Strasse, 3, 37075 Göttingen, Germany; Department of Neurology, University of Göttingen, Robert-Koch-Strasse, 40, 37075 Göttingen, Germany. Electronic address: msimons@gwdg.de.

Abstract

Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally, ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels close with ongoing development but can be reopened in adults by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life.

Comment in

PMID:
24439382
PMCID:
PMC4862569
DOI:
10.1016/j.cell.2013.11.044
[Indexed for MEDLINE]
Free PMC Article
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