Neuronal death in Drosophila triggered by GAL4 accumulation
- 16 February 2007
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 25 (3), 683-694
- https://doi.org/10.1111/j.1460-9568.2007.05317.x
Abstract
The GAL4/UAS system has been extensively employed in Drosophila to control gene expression in defined spatial patterns. More recently this system has been successfully applied to express genes involved in neurodegeneration to model various diseases in the fruit fly. We used transgenic lines expressing different levels of GAL4 in a particular subset of neurons involved in the control of rhythmic behaviour, so that its impact on neuronal physiology would result in altered locomotor activity, which could be readily assessed. We observed a striking correlation between gal4 dosage and behavioural defects associated with apoptotic neuronal loss in the specific GAL4-expressing neurons. Increased gal4 dosage correlated with accumulation of insoluble GAL4, suggesting that the cascade of events leading to apoptosis might be triggered by protein deposits of either GAL4 or protein intermediates. Behavioural defects were rescued by expression of hsp70, a classic chaperone that also interferes with cell death pathways. In agreement with the latter, the viral caspase inhibitor p35 also rescued GAL4-induced behavioural defects. Our observations demonstrate the intrinsic effects of GAL4 deregulation on neuronal viability and suggest that an excess of GAL4 might enhance neuronal deficits observed in models of neurodegenerationKeywords
This publication has 56 references indexed in Scilit:
- A resetting signal between Drosophila pacemakers synchronizes morning and evening activityNature, 2005
- Antiapoptotic and Anti-inflammatory Mechanisms of Heat-Shock Protein ProtectionAnnals of the New York Academy of Sciences, 2005
- Modulation of neurodegeneration by molecular chaperonesNature Reviews Neuroscience, 2005
- Inactivation of Drosophila Apaf-1 related killer suppresses formation of polyglutamine aggregates and blocks polyglutamine pathogenesisHuman Molecular Genetics, 2004
- Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal deathNature, 2004
- Protein aggregation and neurodegenerative diseaseNature Medicine, 2004
- The neuroarchitecture of the circadian clock in the brain of Drosophila melanogasterMicroscopy Research and Technique, 2003
- A Drosophila model of Parkinson's diseaseNature, 2000
- Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in BrainScience, 1997
- GAL4 activates gene expression in mammalian cellsCell, 1988