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Neuron. 2016 Jun 1;90(5):1000-15. doi: 10.1016/j.neuron.2016.04.046. Epub 2016 May 19.

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

Author information

1
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA; Molecular NeuroPathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London, WC1N 3BG, UK.
2
Randall Division of Cell and Molecular Biophysics, King's College London, London, SE1 1UL, UK.
3
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
4
Molecular NeuroPathobiology Laboratory, Sobell Department of Motor Neuroscience & Movement Disorders, UCL Institute of Neurology, University College London, London, WC1N 3BG, UK.
5
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6085, USA. Electronic address: holzbaur@mail.med.upenn.edu.

Abstract

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. VIDEO ABSTRACT.

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PMID:
27210554
PMCID:
PMC4893161
DOI:
10.1016/j.neuron.2016.04.046
[Indexed for MEDLINE]
Free PMC Article

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