Abstract
SummaryCytoplasmic 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
Highlights
In neurons most pre-synaptic proteins are synthesized in the soma and are transported long distances to reach their site of action
In vivo pulse chase labeling experiments identified two major forms of anterograde axonal transport: a fast component (FC) associated with vesicular organelles moving between 50–200 mm/day and a slow component of cytoskeletal and cytoplasmic proteins moving 0.2– 10 mm/day, which can be further subdivided into slow component a (SCa) and slow component b (SCb)
Dynein Preferentially Accumulates in Distal Axons throughout Development As an important first step, we wanted to characterize the distribution of cytoplasmic dynein in our model system of primary hippocampal neurons isolated from the dynein-GFP knockin mouse
Summary
In neurons most pre-synaptic proteins are synthesized in the soma and are transported long distances to reach their site of action. The transit of new axonal and synaptic constituents via slow transport can take up to a year for cells with extended axons such as human motor neurons. At least three times the amount of protein is delivered to pre-synapses by slow compared to fast transport (Garner and Mahler, 1987), making this the major protein delivery system. Instantaneous velocities for neurofilaments are similar to those measured for vesicular cargos, but overall transport rates are dominated by long off-track times in a ‘‘stop and go’’ model for transport (Brown et al, 2005)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
