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Cited by 335Neurogenesis and neuroplasticity mechanismsCellular Mechanics and InteractionsMultiple Sclerosis Research Studies

CNS Myelin Wrapping Is Driven by Actin Disassembly

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Zuchero, J. Bradley, Fu, Meng-meng, Sloan, Steven A., Ibrahim, Adiljan, Olson, Andrew, Zaremba, Anita, Dugas, Jason C., Wienbar, Sophia +9 more·2015·Developmental Cell
DOI 10.1016/j.devcel.2015.06.011PMC PMC4519368
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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.

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  • ARP2/3 complex-mediated actin polymerization is important for the initial phase of oligodendrocyte extension and axonal ensheathment, but rapid myelin wrapping is initiated by F-actin disassembly.

    “ARP2/3 complex-mediated actin polymerization is important for the initial phase of oligodendrocyte extension and axonal ensheathment, but rapid myelin wrapping is initiated by F-actin disassembly4,78.”

    From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [4]

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Authors
Zuchero, J. B., Fu, M.-M., Sloan, S. A., Ibrahim, A., Olson, A., Zaremba, A., Dugas, J. C., Wienbar, S., Caprariello, A. V., Kantor, C., Leonoudakis, D., Lariosa-Willingham, K., Kronenberg, G., Gertz, K., Soderling, S. H., Miller, R. H., & Barres, B. A.
Affiliations
  • Stanford Medicine (US)
  • Case Western Reserve University (US)
  • Myelin Repair Foundation (US)
  • Charité – Universitätsmedizin Berlin (DE)
  • Duke University (US)
Corresponding author
Zuchero, J. Bradley
ORCID
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2015-07
Volume
34
Issue
2
Pages
152-167
ISSN
1534-5807 (ISSN-L)
DOI
10.1016/j.devcel.2015.06.011
PMC
PMC4519368
OpenAlex
W2116747568
Cited by
335
References
3
Citations by year
2026: 21 · 2025: 27 · 2024: 28 · 2023: 19 · 2022: 37 · 2021: 37 · 2020: 39 · 2019: 31 · 2018: 34 · 2017: 35 · 2016: 20 · 2015: 6
FWCI
11.75
Type
journal article
Language
en
Update notices
erratum (2015-09-14)
Open access
Licence
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (1s10rr026780-01)
  • National Institute of Mental Health (F30MH106261, R01MH103374, T32MH020016)
  • National Eye Institute (R01EY010257)
  • National Institute of Neurological Disorders and Stroke (NS069375, R01NS030800, P30NS069375)
  • National Center for Research Resources (1S10RR02678001)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007249)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
oligodendrocytes, actin filament disassembly, Arp2/3 complex, gelsolin, myelin basic protein, actin cytoskeleton, axon ensheathment, myelination
MeSH terms
Actins, Animals, Axons, Cell Membrane, Cell Movement, Cells, Cultured, Central Nervous System, Myelin Basic Protein, Mice, Inbred C57BL, Actin Cytoskeleton, Myelin Sheath, Oligodendroglia, Optic Nerve, Rats, Sprague-Dawley, Gelsolin, Mice, Knockout, RNA Interference, RNA, Small Interfering, Cofilin 1, Actin-Related Protein 2-3 Complex, Mice, Rats

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