The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction
- IBMC/i3S- University of Porto, Portugal
- i3S- Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
- INEB/i3S- University of Porto, Portugal
- Johns Hopkins University School of Medicine, United States
- i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal
- Stowers Institute for Medical Research, United States
- International Iberian Nanotechnology Laboratory, Portugal
- EMBL, Germany
- University of Porto, Portugal
Abstract
Neurons have a membrane periodic skeleton (MPS) composed of actin rings interconnected by spectrin. Here, combining chemical and genetic gain- and loss-of-function assays, we show that in rat hippocampal neurons the MPS is an actomyosin network that controls axonal expansion and contraction. Using super-resolution microscopy, we analyzed the localization of axonal non-muscle myosin II (NMII). We show that active NMII light chains are colocalized with actin rings and organized in a circular periodic manner throughout the axon shaft. In contrast, NMII heavy chains are mostly positioned along the longitudinal axonal axis, being able to crosslink adjacent rings. NMII filaments can play contractile or scaffolding roles determined by their position relative to actin rings and activation state. We also show that MPS destabilization through NMII inactivation affects axonal electrophysiology, increasing action potential conduction velocity. In summary, our findings open new perspectives on axon diameter regulation, with important implications in neuronal biology.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
Fundação para a Ciência e a Tecnologia (NORTE-01-0145-FEDER-028623; PTDC/MED-NEU/28623/2017)
- Monica M Sousa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Experiments were carried out in accordance with the European Union Directive 2010/63/EU and national Decreto-lei nº113-2013. The protocols described were approved by the IBMC Ethical Committee and by the Portuguese Veterinarian Board.
Copyright
© 2020, Costa et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The membrane periodic skeleton is an actomyosin network that regulates axonal diameter and conduction
eLife 9:e55471.
https://doi.org/10.7554/eLife.55471
