title: Genetic defects in β-spectrin and tau sensitizeC. elegansaxons 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 inCaenorhabditis 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.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States.|Department of Chemical Engineering, Stanford University, Stanford, United States.
authors.forename: Michael
authors.identifier: 0000-0003-0501-5036
authors.initials: M
authors.lastname: Krieg
authors.affiliation: Department of Informatics, Technical University of Munich, , Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Stühmer
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States.
authors.forename: Juan G
authors.initials: JG
authors.lastname: Cueva
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Fetter
authors.affiliation: Department of Biology, Stanford University, Stanford, United States.
authors.forename: Kerri
authors.initials: K
authors.lastname: Spilker
authors.affiliation: Department of Informatics, Technical University of Munich, , Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cremers
authors.affiliation: Department of Biology, Stanford University, Stanford, United States.
authors.forename: Kang
authors.identifier: 0000-0003-4059-8249
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Chemical Engineering, Stanford University, Stanford, United States.
authors.forename: Alexander R
authors.identifier: 0000-0001-6096-4600
authors.initials: AR
authors.lastname: Dunn
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University, Stanford, United States.
authors.forename: Miriam B
authors.identifier: 0000-0002-5810-1272
authors.initials: MB
authors.lastname: Goodman
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D008869:Microtubule-Associated Proteins / Q000172:deficiency*; D009068:Movement; D013049:Spectrin / Q000172:deficiency*; D013314:Stress, Mechanical; D019415:Torque; D014404:Tubulin / Q000172:deficiency*
chemical_list: D029742:Caenorhabditis elegans Proteins; C115872:Mec-7 protein, C elegans; D008869:Microtubule-Associated Proteins; C100857:PTL-1 protein, C elegans; D014404:Tubulin; C409166:unc-70 protein, C elegans; D013049:Spectrin
keywords: C. elegans; STED microscopy; axonal mechanics; cell biology; confocal microscopy; cytoskeleton; discrete elastic rods; electron microscopy; neuroscience