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

C Sinadinos, T Burbidge-King, D Soh… - Neurobiology of …, 2009 - Elsevier
C Sinadinos, T Burbidge-King, D Soh, LM Thompson, JL Marsh, A Wyttenbach, AK Mudher
Neurobiology of disease, 2009Elsevier
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 …
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.
Elsevier
Showing the best result for this search. See all results