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CORL Expression and Function in Insulin Producing Neurons Reversibly Influences Adult Longevity in Drosophila
Nancy L Tran1, Samuel L Goldsmith1, Agapi Dimitriadou2
1School of Life Sciences, Arizona State University, Tempe AZ 85287-4501.
Abstract:
CORL proteins (known as SKOR in mice, Fussel in humans and fussel in Flybase) are a family of CNS specific proteins related to Sno/Ski oncogenes. Their developmental and adult roles are largely unknown. A Drosophila CORL (dCORL) reporter gene is expressed in all Drosophila insulin-like peptide 2 (dILP2) neurons of the pars intercerebralis (PI) of the larval and adult brain. The transcription factor Drifter is also expressed in the PI in a subset of dCORL and dILP2 expressing neurons and in several non-dILP2 neurons. dCORL mutant virgin adult brains are missing all dILP2 neurons that do not also express Drifter. This phenotype is also seen when expressing dCORL-RNAi in neurosecretory cells of the PI. dCORL mutant virgin adults of both sexes have a significantly shorter lifespan than their parental strain. This longevity defect is completely reversed by mating (lifespan increases over 50% for males and females). Analyses of dCORL mutant mated adult brains revealed a complete rescue of dILP2 neurons without Drifter. Taken together, the data suggest that dCORL participates in a neural network connecting the insulin signaling pathway, longevity and mating. The conserved sequence and CNS specificity of all CORL proteins imply that this network may be operating in mammals.
Insights
The CORL protein is crucial for maintaining specific neurons in the brain, impacting lifespan and mating behaviors in fruit flies. Its absence shortens lifespan, which mating can reverse.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- CORL proteins, related to Sno/Ski oncogenes, are CNS-specific with largely unknown functions.
- A Drosophila CORL (dCORL) reporter gene is expressed in insulin-like peptide 2 (dILP2) neurons within the pars intercerebralis (PI).
Purpose of the Study:
- To investigate the role of dCORL in the development and function of dILP2 neurons.
- To explore the connection between dCORL, lifespan, and mating behavior in Drosophila.
Main Methods:
- Utilized dCORL reporter gene expression analysis.
- Generated and analyzed dCORL mutant fruit flies.
- Performed RNA interference (RNAi) in neurosecretory cells of the PI.
- Assessed lifespan and neuronal phenotypes in mutant and wild-type flies.
Main Results:
- dCORL mutant brains showed a loss of dILP2 neurons lacking the transcription factor Drifter.
- This neuronal loss was replicated by dCORL-RNAi in PI neurosecretory cells.
- dCORL mutant virgin adults exhibited significantly shorter lifespans, which were rescued by mating.
- Mated dCORL mutant brains displayed a rescue of dILP2 neurons.
Conclusions:
- dCORL plays a role in a neural network involving insulin signaling, longevity, and mating.
- The findings suggest a conserved function for CORL proteins in mammals, potentially linking CNS function, lifespan, and reproduction.
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