title: CNS myelin wrapping is driven by actin disassembly.
abstract: Myelin is essential in vertebrates for the rapid propagation of action potentials, but the molecular mechanisms driving its formation remain largely unknown. Here we show that the initial stage of process extension and axon ensheathment by oligodendrocytes requires dynamic actin filament assembly by the Arp2/3 complex. Unexpectedly, subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins and rapid disassembly of the oligodendrocyte actin cytoskeleton and does not require Arp2/3. Inducing loss of actin filaments drives oligodendrocyte membrane spreading and myelin wrapping in vivo, and the actin disassembly factor gelsolin is required for normal wrapping. We show that myelin basic protein, a protein essential for CNS myelin wrapping whose role has been unclear, is required for actin disassembly, and its loss phenocopies loss of actin disassembly proteins. Together, these findings provide insight into the molecular mechanism of myelin wrapping and identify it as an actin-independent form of mammalian cell motility.
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: brad.zuchero@gmail.com.
authors.forename: J Bradley
authors.initials: JB
authors.lastname: Zuchero
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Meng-Meng
authors.initials: MM
authors.lastname: Fu
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Sloan
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Adiljan
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Olson
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Zaremba
authors.affiliation: Myelin Repair Foundation, Saratoga, CA 95070, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Dugas
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Wienbar
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Caprariello
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kantor
authors.forename: Dmitri
authors.initials: D
authors.lastname: Leonoudakis
authors.affiliation: Myelin Repair Foundation, Saratoga, CA 95070, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Leonoudakus
authors.affiliation: Myelin Repair Foundation, Saratoga, CA 95070, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Lariosa-Willingham
authors.affiliation: Klinik für Psychiatrie und Psychotherapie, Charité-Universitätsmedizin Berlin, Charité Campus Mitte, 10117 Berlin, Germany; Klinik und Poliklinik für Neurologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Golo
authors.initials: G
authors.lastname: Kronenberg
authors.affiliation: Klinik und Poliklinik für Neurologie, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Gertz
authors.affiliation: Departments of Cell Biology and Neurobiology, Duke University Medical School, Durham, NC 27710, USA.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Soderling
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Miller
authors.affiliation: Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development*; D051338:Cofilin 1 / Q000235:genetics; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C495811:Cfl1 protein, mouse; D051338:Cofilin 1; D018260:Gelsolin; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D034741:RNA, Small Interfering