title: Actin filament turnover drives leading edge growth during myelin sheath formation in the central nervous system.
abstract: During CNS development, oligodendrocytes wrap their plasma membrane around axons to generate multilamellar myelin sheaths. To drive growth at the leading edge of myelin at the interface with the axon, mechanical forces are necessary, but the underlying mechanisms are not known. Using an interdisciplinary approach that combines morphological, genetic, and biophysical analyses, we identified a key role for actin filament network turnover in myelin growth. At the onset of myelin biogenesis, F-actin is redistributed to the leading edge, where its polymerization-based forces push out non-adhesive and motile protrusions. F-actin disassembly converts protrusions into sheets by reducing surface tension and in turn inducing membrane spreading and adhesion. We identified the actin depolymerizing factor ADF/cofilin1, which mediates high F-actin turnover rates, as an essential factor in this process. We propose that F-actin turnover is the driving force in myelin wrapping by regulating repetitive cycles of leading edge protrusion and spreading.
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Schanila
authors.initials: S
authors.lastname: Nawaz
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.|III. Physics Institute, Faculty of Physics, University of Göttingen, 37077 Göttingen, Germany.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Sánchez
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schmitt
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Snaidero
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Mišo
authors.initials: M
authors.lastname: Mitkovski
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Velte
authors.affiliation: Institute for Physical Chemistry, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Bastian R
authors.initials: BR
authors.lastname: Brückner
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Alexopoulos
authors.affiliation: Centre for Neuroregeneration, Chancellor's Building, GU 507B, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Czopka
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Sang Y
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Jeong S
authors.initials: JS
authors.lastname: Rhee
authors.affiliation: Institute for Physical Chemistry, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Janshoff
authors.affiliation: Institute of Genetics, University of Bonn, Karlrobert-Kreiten Strasse 13, 53115 Bonn, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Witke
authors.affiliation: III. Physics Institute, Faculty of Physics, University of Göttingen, 37077 Göttingen, Germany.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Göttingen, Germany.
authors.forename: Iwan A T
authors.initials: IAT
authors.lastname: Schaap
authors.affiliation: Centre for Neuroregeneration, Chancellor's Building, GU 507B, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Lyons
authors.affiliation: Max Planck Institute for Experimental Medicine, 37075 Göttingen, Germany.|Department of Neurology, University of Göttingen, 37075 Göttingen, Germany.
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000199:Actins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development*; D051338:Cofilin 1 / Q000235:genetics / Q000378:metabolism*; D051345:Destrin / Q000235:genetics / Q000378:metabolism*; D008164:Luminescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology; D018408:Patch-Clamp Techniques; D013500:Surface Tension; D015027:Zebrafish; D000097573:Red Fluorescent Protein
chemical_list: D000199:Actins; D051338:Cofilin 1; D051345:Destrin; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C495811:Cfl1 protein, mouse; C495825:Dstn protein, mouse