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Cited by 49Neurogenesis and neuroplasticity mechanismsMultiple Sclerosis Research StudiesNeuroscience and Neuropharmacology Research

Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

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Iyer, Manasi, Kantarci, Husniye, Cooper, Madeline H., Ambiel, Nicholas, Novak, Sammy Weiser, Andrade, Leonardo R., Lam, Mable, Jones, Graham +5 more·2024·Nature Communications
DOI 10.1038/s41467-023-44238-3PMC PMC10767123

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Abstract

Myelin is essential for rapid nerve signaling and is increasingly found to play important roles in learning and in diverse diseases of the CNS. Morphological parameters of myelin such as sheath length are thought to precisely tune conduction velocity, but the mechanisms controlling sheath morphology are poorly understood. Local calcium signaling has been observed in nascent myelin sheaths and can be modulated by neuronal activity. However, the role of calcium signaling in sheath formation remains incompletely understood. Here, we use genetic tools to attenuate oligodendrocyte calcium signaling during myelination in the developing mouse CNS. Surprisingly, genetic calcium attenuation does not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation causes myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduces actin filaments in oligodendrocytes, and an intact actin cytoskeleton is necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a cellular mechanism required for accurate CNS myelin formation and may provide mechanistic insight into how oligodendrocytes respond to neuronal activity to sculpt and refine myelin sheaths.

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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 [78]

    The Results section (page unavailable) identifies Arp2/3 as an actin-nucleating complex necessary for early myelination. The Discussion (page unavailable) says actin assembly is required for oligodendrocytes to extend processes and ensheath axons, while subsequent wrapping requires actin disassembly. It does not establish that disassembly initiates wrapping or that the wrapping is rapid. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Iyer, M., Kantarci, H., Cooper, M. H., Ambiel, N., Novak, S. W., Andrade, L. R., Lam, M., Jones, G., Münch, A. E., Yu, X., Khakh, B. S., Manor, U., & Zuchero, J. B.
Affiliations
  • Stanford Medicine (US)
  • Salk Institute for Biological Studies (US)
  • University of Illinois Urbana-Champaign (US)
  • University of California, Los Angeles (US)
Corresponding author
Zuchero, J. Bradley
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-01-04
Volume
15
Issue
1
Pages
265-265
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-44238-3
PMC
PMC10767123
OpenAlex
W4390587977
Cited by
49
References
8
Citations by year
2026: 18 · 2025: 19 · 2024: 12
FWCI
7.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • PubMed Central (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • McKnight Endowment Fund for Neuroscience
  • National Multiple Sclerosis Society
  • SU | Stanford Bio-X
  • Arnold and Mabel Beckman Foundation
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
myelination, actin cytoskeleton, myelination defects, neuronal activity, oligodendrocytes, central nervous system development, myelinated axons

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