Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons
| Autor: | Amritpal Mudher, T. Burbidge-King, J.L. Marsh, Leslie M. Thompson, Andreas Wyttenbach, D. Soh, Christopher Sinadinos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Central Nervous System
Male Huntington's Disease Huntingtin Mutant Video microscopy Nerve Tissue Proteins Biology Heat Stress Disorders N-terminal huntingtin Body Temperature lcsh:RC321-571 Huntington's disease Stress Physiological mental disorders medicine Animals Humans Transport Vesicles lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Gait Disorders Neurologic Motor neurons Axonal transport Huntingtin Protein Vesicle Nuclear Proteins Motor neuron medicine.disease Axons Cell biology Vesicular transport protein neuropeptide-Y medicine.anatomical_structure Huntington Disease Neurology nervous system Axoplasmic transport Female Drosophila Peptides Neuroscience |
| Zdroj: | Neurobiology of Disease, Vol 34, Iss 2, Pp 389-395 (2009) Sinadinos, C; Burbidge-King, T; Soh, D; Thompson, LM; Marsh, JL; Wyttenbach, A; et al.(2009). Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons. Neurobiology of Disease, 34(2), 389-395. doi: 10.1016/j.nbd.2009.02.012. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/30g9v0dv |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|