髓鞘
少突胶质细胞
钙
细胞生物学
生物
钙信号传导
神经科学
细胞骨架
信号转导
中枢神经系统
化学
细胞
生物化学
有机化学
作者
Manasi Iyer,Husniye Kantarci,Nicholas Ambiel,Sammy Weiser Novak,Leonardo R. Andrade,Mable Lam,Alexandra E. Münch,Xinzhu Yu,Baljit S. Khakh,Uri Manor,J. Bradley Zuchero
标识
DOI:10.1101/2023.04.11.536299
摘要
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 and thickness are regulated by neuronal activity and can 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 and remodeling is unknown. Here, we used genetic tools to attenuate oligodendrocyte calcium signaling during active myelination in the developing mouse CNS. Surprisingly, we found that genetic calcium attenuation did not grossly affect the number of myelinated axons or myelin thickness. Instead, calcium attenuation caused striking myelination defects resulting in shorter, dysmorphic sheaths. Mechanistically, calcium attenuation reduced actin filaments in oligodendrocytes, and an intact actin cytoskeleton was necessary and sufficient to achieve accurate myelin morphology. Together, our work reveals a novel cellular mechanism required for accurate CNS myelin formation and provides mechanistic insight into how oligodendrocytes may respond to neuronal activity to sculpt myelin sheaths throughout the nervous system.
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