Actomyosin-II protects axons from degeneration induced by mild mechanical stress
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Date
2024
Authors
Pan, X.
Hu, Y.
Lei, G.
Wei, Y.
Li, J.
Luan, T.
Zhang, Y.
Chu, Y.
Feng, Y.
Zhan, W.
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Journal article
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Journal of Cell Biology, 2024; 223(8):e202206046-1-e202206046-32
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Xiaorong Pan, Yiqing Hu, Gaowei Lei, Yaxuan Wei, Jie Li, Tongshu Luan, Yunfan Zhang, Yuanyuan Chu, Yu Feng, Wenrong Zhan, Chunxia Zhao, Frédéric A. Meunier, Yifan Liu, Yi Li, Tong Wang
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Abstract
Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.
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© 2024 Pan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).