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First published online October 22, 2003
doi: 10.1242/10.1242/jcs.00727

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Myosin Va and microtubule-based motors are required for fast axonal retrograde transport of tetanus toxin in motor neurons

Giovanna Lalli^1,*, Stephen Gschmeissner² and Giampietro Schiavo^1,

¹ Molecular NeuroPathoBiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK
² Electron Microscopy Unit, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

Author for correspondence (e-mail: giampietro.schiavo{at}cancer.org.uk)

Accepted 27 June 2003

Using a novel assay based on the sorting and transport of a fluorescent fragment of tetanus toxin, we have investigated the cytoskeletal and motor requirements of axonal retrograde transport in living mammalian motor neurons. This essential process ensures the movement of neurotrophins and organelles from the periphery to the cell body and is crucial for neuronal survival. Unlike what is observed in sympathetic neurons, fast retrograde transport in motor neurons requires not only intact microtubules, but also actin microfilaments. Here, we show that the movement of tetanus toxin-containing carriers relies on the nonredundant activities of dynein as well as kinesin family members. Quantitative kinetic analysis indicates a role for dynein as the main motor of these carriers. Moreover, this approach suggests the involvement of myosin(s) in retrograde movement. Immunofluorescence screening with isoform-specific myosin antibodies reveals colocalization of tetanus toxin-containing retrograde carriers with myosin Va. Motor neurons from homozygous myosin Va null mice showed slower retrograde transport compared with wild-type cells, establishing a unique role for myosin Va in this process. On the basis of our findings, we propose that coordination of myosin Va and microtubule-dependent motors is required for fast axonal retrograde transport in motor neurons.

Key words: Axonal transport, Motor neuron, Myosin Va, Neuronal cytoskeleton, Tetanus toxin

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