Reference Report

Reference
Citation	Luo, J., Becnel, J., Nichols, C.D., Nässel, D.R. (2012). Insulin-producing cells in the brain of adult Drosophila are regulated by the serotonin 5-HT(1A) receptor. Cell. Molec. Life Sci. 69(3): 471--484. (Export to RIS)
FlyBase ID	FBrf0217219
Publication Type	Research paper
PubMed ID	21818550
PubMed 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.
DOI	10.1007/s00018-011-0789-0
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Cell. Molec. Life Sci.
Title	Cellular and molecular life sciences. CMLS
Publication Year	1997-
ISBN/ISSN	1420-682X
Data from Reference
Alleles (14)
	5-HT1A^{dsRNA.Scer\UAS} 5-HT1A^KK108407 5-HT1A^Δ5kb 5-HT7^Scer\UAS.cKa Avic\GFP^{S65T.Scer\UAS} Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Scer\GAL4^5-HT1A.ERGP Scer\GAL4^5-HT1B.PY Scer\GAL4^5-HT7.ERGP Scer\GAL4^Act5C.PI Scer\GAL4^ey-OK107 Scer\GAL4^Ilp2.215-3 Scer\GAL4^Ilp2.PW Scer\GAL4^l.Trh.PK
Constructs (12)
	P{5-HT1A-GAL4.L} P{5-HT7-GAL4.B} P{Act5C-GAL4} P{GAL4-5-HT1B.Y} P{Ilp2-GAL4.215-3} P{Ilp2-GAL4.W} P{KK108407} P{Trh-GAL4.long} P{UAS-5-HT1A.dsRNA} P{UAS-5-HT7.K} P{UAS-GFP.S65T} P{UAS-mCD8::GFP.L}
Genes (8)
	5-HT1A 5-HT1B 5-HT7 Avic\GFP Ilp2 Mmus\Cd8a Oamb Scer\GAL4
Insertions (1)
	P{GawB}ey^OK107
Natural transposons (1)
	P-element