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First published online 21 September 2005
doi: 10.1242/jcs.02558
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Research Article |
-synuclein
Department of Neuroscience, King's College London, Institute of Psychiatry, De Crespigny Park, London, SE5 8AF, UK
* Author for correspondence (e-mail: b.anderton{at}iop.kcl.ac.uk)
Accepted 22 June 2005
Tau and 
-synuclein are both proteins implicated in the pathology of neurodegenerative disease. Here we have investigated the mechanisms of axonal transport of tau and -synuclein, because failure of axonal transport has been implicated in the development of several neurodegenerative disorders. We found that the transport of both of these proteins depend on an intact microtubule- but not actin-cytoskeleton, and that tau and -synuclein both move at overall slow rates of transport. We used time-lapse video microscopy to obtain images of live neurons that had been transfected with plasmids expressing proteins tagged with enhanced green fluorescent protein. We found that particulate structures containing tau or -synuclein travel rapidly when moving along axons but spend the majority of the time paused, and these structures have similar characteristics to those previously observed for neurofilaments. The motile particles containing tau or -synuclein colocalise with the fast-transporting molecular motor kinesin-1 in neurons. Co-immunoprecipitation experiments demonstrate that tau and -synuclein are each associated with complexes containing kinesin-1, whereas only -synuclein appears to interact with dynein-containing complexes. In vitro glutathione S-transferase-binding assays using rat brain homogenate or recombinant protein as bait reveals a direct interaction of kinesin-1 light chains 1 and 2 with tau, but not with -synuclein. Our findings suggest that the axonal transport of tau occurs via a mechanism utilising fast transport motors, including the kinesin family of proteins, and that -synuclein transport in neurons may involve both kinesin and dynein motor proteins.
Key words: Tau, -Synuclein, Axonal transport, Kinesin, Dynein, Glutathione S-transferase
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