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

Alison E Twelvetrees, Stefano Pernigo, Anneri Sanger, Pedro Guedes-Dias, Giampietro Schiavo, Roberto A Steiner, Mark P Dodding, Erika L F Holzbaur

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.

Original languageEnglish
Pages (from-to)1000-1015
Number of pages16
JournalNeuron
Volume90
Issue number5
Early online date19 May 2016
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Animals
  • Axonal Transport
  • Cells, Cultured
  • Cytoplasmic Dyneins
  • Dyneins
  • Gene Knock-In Techniques
  • Hippocampus
  • Kinesin
  • Mice
  • Neurites
  • Journal Article

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