eprintid: 1493075 rev_number: 35 eprint_status: archive userid: 608 dir: disk0/01/49/30/75 datestamp: 2016-06-16 13:47:16 lastmod: 2021-09-26 22:59:20 status_changed: 2016-06-16 13:47:16 type: article metadata_visibility: show creators_name: Twelvetrees, AE creators_name: Pernigo, S creators_name: Sanger, A creators_name: Guedes-Dias, P creators_name: Schiavo, G creators_name: Steiner, RA creators_name: Dodding, MP creators_name: Holzbaur, EL title: The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1 ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F85 note: Copyright © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) 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. date: 2016-06-01 date_type: published official_url: http://dx.doi.org/10.1016/j.neuron.2016.04.046 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1130494 doi: 10.1016/j.neuron.2016.04.046 pii: S0896-6273(16)30160-X lyricists_name: Schiavo, Giampietro lyricists_name: Twelvetrees, Alison lyricists_id: GSCHI71 lyricists_id: AETWE75 actors_name: Twelvetrees, Alison actors_id: AETWE75 actors_role: owner full_text_status: public publication: Neuron volume: 90 number: 5 pagerange: 1000-1015 issn: 1097-4199 citation: Twelvetrees, AE; Pernigo, S; Sanger, A; Guedes-Dias, P; Schiavo, G; Steiner, RA; Dodding, MP; Twelvetrees, AE; Pernigo, S; Sanger, A; Guedes-Dias, P; Schiavo, G; Steiner, RA; Dodding, MP; Holzbaur, EL; - view fewer <#> (2016) The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1. Neuron , 90 (5) pp. 1000-1015. 10.1016/j.neuron.2016.04.046 <https://doi.org/10.1016/j.neuron.2016.04.046>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1493075/1/Twelvetrees%20et%20al%202016%20Dynamic%20localization.pdf