Axons break in animals lacking beta-spectrin.
Axons and dendrites can withstand acute mechanical strain despite their small diameter. In this study, we demonstrate that beta-spectrin is required for the physical integrity of neuronal processes in the nematode Caenorhabditis elegans. Axons in beta-spectrin mutants spontaneously break. Breakage is caused by acute strain generated by movement because breakage can be prevented by paralyzing the mutant animals. After breaking, the neuron attempts to regenerate by initiating a new growth cone; this second round of axon extension is error prone compared with initial outgrowth. Because spectrin is a major target of calpain proteolysis, it is possible that some neurodegenerative disorders may involve the cleavage of spectrin followed by the breakage of neural processes.
Hammarlund
Marc
M
Department of Biology, Howard Hughes Medical Institute, University of Utah, Salt Lake City, UT 84112, USA.
Jorgensen
Erik M
EM
Bastiani
Michael J
MJ
D000818:Animals; D001369:Axons / Q000473:pathology* / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004548:Elasticity; D009068:Movement; D009154:Mutation; D009422:Nervous System Diseases / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D010641:Phenotype; D013049:Spectrin / Q000235:genetics*; D013314:Stress, Mechanical
D029742:Caenorhabditis elegans Proteins; C409166:unc-70 protein, C elegans; D013049:Spectrin