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Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT1A receptor.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2012 Feb; Vol. 69 (3), pp. 471-84. Date of Electronic Publication: 2011 Aug 05. - Publication Year :
- 2012
-
Abstract
- Insulin signaling regulates lifespan, reproduction, metabolic homeostasis, and resistance to stress in the adult organism. In Drosophila, there are seven insulin-like peptides (DILP1-7). Three of these (DILP2, 3 and 5) are produced in median neurosecretory cells of the brain, designated IPCs. Previous work has suggested that production or release of DILPs in IPCs can be regulated by a factor secreted from the fat body as well as by neuronal GABA or short neuropeptide F. There is also evidence that serotonergic neurons may regulate IPCs. Here, we investigated mechanisms by which serotonin may regulate the IPCs. We show that the IPCs in adult flies express the 5-HT(1A), but not the 5-HT(1B) or 5-HT(7) receptors, and that processes of serotonergic neurons impinge on the IPC branches. Knockdown of 5-HT(1A) in IPCs by targeted RNA interference (RNAi) leads to increased sensitivity to heat, prolonged recovery after cold knockdown and decreased resistance to starvation. Lipid metabolism is also affected, but no effect on growth was seen. Furthermore, we show that DILP2-immunolevels in IPCs increase after 5-HT(1A) knockdown; this is accentuated by starvation. Heterozygous 5-HT(1A) mutant flies display the same phenotype in all assays, as seen after targeted 5-HT(1A) RNAi, and flies fed the 5-HT(1A) antagonist WAY100635 display reduced lifespan at starvation. Our findings suggest that serotonin acts on brain IPCs via the 5-HT(1A) receptor, thereby affecting their activity and probably insulin signaling. Thus, we have identified a second inhibitory pathway regulating IPC activity in the Drosophila brain.
- Subjects :
- Animals
Drosophila
Drosophila Proteins antagonists & inhibitors
Drosophila Proteins genetics
Insulin metabolism
Insulin-Secreting Cells drug effects
Lipid Metabolism
Male
Piperazines pharmacology
Pyridines pharmacology
RNA Interference
Receptor, Serotonin, 5-HT1A chemistry
Receptor, Serotonin, 5-HT1A genetics
Serotonin 5-HT1 Receptor Antagonists pharmacology
Signal Transduction drug effects
Stress, Physiological
Brain cytology
Drosophila Proteins metabolism
Insulin-Secreting Cells metabolism
Receptor, Serotonin, 5-HT1A metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 69
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 21818550
- Full Text :
- https://doi.org/10.1007/s00018-011-0789-0