Genetic defects in β-spectrin and tau sensitize C. elegans axons to movement-induced damage via torque-tension coupling
Abstract
Our bodies are in constant motion and so are the neurons that invade each tissue. Motion-induced neuron deformation and damage are associated with several neurodegenerative conditions. Here, we investigated the question of how the neuronal cytoskeleton protects axons and dendrites from mechanical stress, exploiting mutations in UNC-70 β-spectrin, PTL-1 tau/MAP2-like and MEC-7 β-tubulin proteins in Caenorhabditis elegans. We found that mechanical stress induces supercoils and plectonemes in the sensory axons of spectrin and tau double mutants. Biophysical measurements, super-resolution and electron microscopy, as well as numerical simulations of neurons as discrete, elastic rods provide evidence that a balance of torque, tension, and elasticity stabilizes neurons against mechanical deformation. We conclude that the spectrin and microtubule cytoskeletons work in combination to protect axons and dendrites from mechanical stress, and propose that defects in -spectrin and tau may sensitize neurons to damage.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (R01NS092099-02)
- Alexander R Dunn
- Miriam B Goodman
National Institute of Neurological Disorders and Stroke (5K99NS089942-02)
- Michael Krieg
Howard Hughes Medical Institute
- Kang Shen
- Alexander R Dunn
H2020 European Research Council (ERC-2014-CoG)
- Jan Stühmer
- Daniel Cremers
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Krieg 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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