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| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Nature neuroscience
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39623218/ |
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Table of Contents:
- Membrane mechanics dictate axonal pearls-on-a-string morphology and function. Griswold, Jacqueline M Bonilla-Quintana, Mayte Pepper, Renee Lee, Christopher T Raychaudhuri, Sumana Ma, Siyi Gan, Quan Syed, Sarah Zhu, Cuncheng Bell, Miriam Suga, Mitsuo Yamaguchi, Yuuki Chéreau, Ronan Nägerl, U Valentin Knott, Graham Rangamani, Padmini Watanabe, Shigeki Animals Axons Mice Cell Membrane Action Potentials Mice, Inbred C57BL Cholesterol Male Female Neural Conduction Axons are ultrathin membrane cables that are specialized for the conduction of action potentials. Although their diameter is variable along their length, how their morphology is determined is unclear. Here, we demonstrate that unmyelinated axons of the mouse central nervous system have nonsynaptic, nanoscopic varicosities ~200 nm in diameter repeatedly along their length interspersed with a thin cable ~60 nm in diameter like pearls-on-a-string. In silico modeling suggests that this axon nanopearling can be explained by membrane mechanical properties. Treatments disrupting membrane properties, such as hyper- or hypotonic solutions, cholesterol removal and nonmuscle myosin II inhibition, alter axon nanopearling, confirming the role of membrane mechanics in determining axon morphology. Furthermore, neuronal activity modulates plasma membrane cholesterol concentration, leading to changes in axon nanopearls and causing slowing of action potential conduction velocity. These data reveal that biophysical forces dictate axon morphology and function, and modulation of membrane mechanics likely underlies unmyelinated axonal plasticity.