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Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

Author

Listed:
  • Manasi Iyer

    (Stanford University School of Medicine)

  • Husniye Kantarci

    (Stanford University School of Medicine)

  • Madeline H. Cooper

    (Stanford University School of Medicine)

  • Nicholas Ambiel

    (Stanford University School of Medicine)

  • Sammy Weiser Novak

    (Salk Institute for Biological Studies)

  • Leonardo R. Andrade

    (Salk Institute for Biological Studies)

  • Mable Lam

    (Stanford University School of Medicine)

  • Graham Jones

    (Stanford University School of Medicine)

  • Alexandra E. Münch

    (Stanford University School of Medicine)

  • Xinzhu Yu

    (University of Illinois at Urbana-
    University of California, Los Angeles)

  • Baljit S. Khakh

    (University of California, Los Angeles)

  • Uri Manor

    (Salk Institute for Biological Studies
    University of California, San Diego)

  • J. Bradley Zuchero

    (Stanford University School of Medicine)

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.

Suggested Citation

  • Manasi Iyer & Husniye Kantarci & Madeline H. Cooper & Nicholas Ambiel & Sammy Weiser Novak & Leonardo R. Andrade & Mable Lam & Graham Jones & Alexandra E. Münch & Xinzhu Yu & Baljit S. Khakh & Uri Man, 2024. "Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44238-3
    DOI: 10.1038/s41467-023-44238-3
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    References listed on IDEAS

    as
    1. Ricardo E. Dolmetsch & Richard S. Lewis & Christopher C. Goodnow & James I. Healy, 1997. "Differential activation of transcription factors induced by Ca2+ response amplitude and duration," Nature, Nature, vol. 388(6639), pages 308-308, July.
    2. Mable Lam & Koji Takeo & Rafael G. Almeida & Madeline H. Cooper & Kathryn Wu & Manasi Iyer & Husniye Kantarci & J. Bradley Zuchero, 2022. "CNS myelination requires VAMP2/3-mediated membrane expansion in oligodendrocytes," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    3. Ricardo E. Dolmetsch & Richard S. Lewis & Christopher C. Goodnow & James I. Healy, 1997. "Differential activation of transcription factors induced by Ca2+ response amplitude and duration," Nature, Nature, vol. 386(6627), pages 855-858, April.
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