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Axons Break in Animals Lacking Β-Spectrin

MarcHammarlund,ErikM.Jorgensen,MichaelJ.Bastiani

Abstract

Axons and dendrites can withstand acute mechanical strain despite their small diameter. In this study, we demonstrate that β-spectrin is required for the physical integrity of neuronal processes in the nematodeCaenorhabditiselegans. Axons in β-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.