Neuron
Volume 90, Issue 5, 1 June 2016, Pages 1000-1015
Journal home page for Neuron

Article
The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1

https://doi.org/10.1016/j.neuron.2016.04.046Get rights and content
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Highlights

  • Dynein localization is dynamic prior to axon specification

  • Dynein is enriched distally in axons via slow axonal transport

  • Anterograde trafficking of dynein is driven by a direct interaction with kinesin-1

  • Slow transport of cytosolic cargos involves transient links to processive motors

Summary

Cytoplasmic dynein, the major motor driving retrograde axonal transport, must be actively localized to axon terminals. This localization is critical as dynein powers essential retrograde trafficking events required for neuronal survival, such as neurotrophic signaling. Here, we demonstrate that the outward transport of dynein from soma to axon terminal is driven by direct interactions with the anterograde motor kinesin-1. In developing neurons, we find that dynein dynamically cycles between neurites, following kinesin-1 and accumulating in the nascent axon coincident with axon specification. In established axons, dynein is constantly transported down the axon at slow axonal transport speeds; inhibition of the kinesin-1-dynein interaction effectively blocks this process. In vitro and live-imaging assays to investigate the underlying mechanism lead us to propose a new model for the slow axonal transport of cytosolic cargos, based on short-lived direct interactions of cargo with a highly processive anterograde motor.

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