Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States; Department of Chemical Engineering, Stanford University, Stanford, United States
Jan Stühmer
Department of Informatics, Technical University of Munich, Germany
Juan G Cueva
Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States
Richard Fetter
Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States
Kerri Spilker
Department of Biology, Stanford University, Stanford, United States
Daniel Cremers
Department of Informatics, Technical University of Munich, Germany
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 β-spectrin and tau may sensitize neurons to damage.
