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Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons

By Christopher Sinadinos, T. Burbidge-King, D. Soh, L.M. Thompson, J.L Marsh, Andreas Wyttenbach and Amritpal Mudher


Huntington's Disease is a neurodegenerative condition caused by a polyglutamine expansion in the<br/>huntingtin (Htt) protein, which aggregates and also causes neuronal dysfunction. Pathogenic N-terminal htt<br/>fragments perturb axonal transport in vitro. To determine whether this occurs in vivo and to elucidate how<br/>transport is affected, we expressed htt exon 1 with either pathogenic (HttEx1Q93) or non-pathogenic (HttEx1Q20) polyglutamine tracts in Drosophila. We found that HttEx1Q93 expression causes axonal<br/>accumulation of GFP-tagged fast axonal transport vesicles in vivo and leads to aggregates within larval motor<br/>neuron axons. Time-lapse video microscopy, shows that vesicle velocity is unchanged in HttEx1Q93-axons<br/>compared to HttEx1Q20-axons, but vesicle stalling occurs to a greater extent. Whilst HttEx1Q93 expression<br/>did not affect locomotor behaviour, external heat stress unveiled a locomotion deficit in HttEx1Q93 larvae.<br/>Therefore vesicle transport abnormalities amidst axonal htt aggregation places a cumulative burden upon<br/>normal neuronal function under stressful conditions

Year: 2009
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Provided by: e-Prints Soton

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