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

TY - JOUR

T1 - The Dynamic Localization of Cytoplasmic Dynein in Neurons Is Driven by Kinesin-1

AU - Twelvetrees, Alison E.

AU - Pernigo, Stefano

AU - Sanger, Anneri

AU - Guedes-Dias, Pedro

AU - Schiavo, Giampietro

AU - Steiner, Roberto A.

AU - Dodding, Mark P.

AU - Holzbaur, Erika L.F.

PY - 2016/5/19

Y1 - 2016/5/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84975461074&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2016.04.046

DO - 10.1016/j.neuron.2016.04.046

M3 - Article

SN - 0896-6273

JO - Neuron

JF - Neuron

ER -