Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons
- Author(s): Sinadinos, C
- Burbidge-King, T
- Soh, D
- Thompson, LM
- Marsh, JL
- Wyttenbach, A
- Mudher, AK
- et al.
Published Web Locationhttps://doi.org/10.1016/j.nbd.2009.02.012
Huntington's Disease is a neurodegenerative condition caused by a polyglutamine expansion in the huntingtin (Htt) protein, which aggregates and also causes neuronal dysfunction. Pathogenic N-terminal htt fragments perturb axonal transport in vitro. To determine whether this occurs in vivo and to elucidate how 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 accumulation of GFP-tagged fast axonal transport vesicles in vivo and leads to aggregates within larval motor neuron axons. Time-lapse video microscopy, shows that vesicle velocity is unchanged in HttEx1Q93-axons compared to HttEx1Q20-axons, but vesicle stalling occurs to a greater extent. Whilst HttEx1Q93 expression did not affect locomotor behaviour, external heat stress unveiled a locomotion deficit in HttEx1Q93 larvae. Therefore vesicle transport abnormalities amidst axonal htt aggregation places a cumulative burden upon normal neuronal function under stressful conditions. © 2009 Elsevier Inc. All rights reserved.
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