Neuron
Volume 92, Issue 4, 23 November 2016, Pages 845-856
Journal home page for Neuron

Article
Branch-Specific Microtubule Destabilization Mediates Axon Branch Loss during Neuromuscular Synapse Elimination

https://doi.org/10.1016/j.neuron.2016.09.049Get rights and content
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Highlights

  • During synapse elimination, retreating axon branches dismantle their microtubules

  • Microtubules are destabilized due to branch-specific severing

  • Microtubule stabilization delays axon branch removal during synapse elimination

  • The disease-associated microtubule severing protein spastin mediates microtubule loss

Summary

Developmental axon remodeling is characterized by the selective removal of branches from axon arbors. The mechanisms that underlie such branch loss are largely unknown. Additionally, how neuronal resources are specifically assigned to the branches of remodeling arbors is not understood. Here we show that axon branch loss at the developing mouse neuromuscular junction is mediated by branch-specific microtubule severing, which results in local disassembly of the microtubule cytoskeleton and loss of axonal transport in branches that will subsequently dismantle. Accordingly, pharmacological microtubule stabilization delays neuromuscular synapse elimination. This branch-specific disassembly of the cytoskeleton appears to be mediated by the microtubule-severing enzyme spastin, which is dysfunctional in some forms of upper motor neuron disease. Our results demonstrate a physiological role for a neurodegeneration-associated modulator of the cytoskeleton, reveal unexpected cell biology of branch-specific axon plasticity and underscore the mechanistic similarities of axon loss in development and disease.

Keywords

synapse elimination
neuromuscular junction
axonal transport
microtubule
cytoskeleton

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