Oligodendrocyte calcium signaling promotes actin-dependent myelin sheath extension

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 Manor, J. Bradley Zuchero

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Article number265
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

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