Myelin Membrane Wrapping of CNS Axons by PI(3,4,5)P3-Dependent Polarized Growth at the Inner Tongue

Nicolas Snaidero, Wiebke Möbius, Tim Czopka, Liesbeth H. P. Hekking, Cliff Mathisen, Dick Verkleij, Sandra Goebbels, Julia Edgar, Doron Merkler, David A. Lyons, Klaus-Armin Nave, Mikael Simons

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Pages (from-to)277-290
Number of pages14
Issue number1-2
Early online date16 Jan 2014
Publication statusE-pub ahead of print - 16 Jan 2014


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