Reference Report

Reference
Citation	Enell, L.E., Kapan, N., Söderberg, J.A., Kahsai, L., Nässel, D.R. (2010). Insulin Signaling, Lifespan and Stress Resistance Are Modulated by Metabotropic GABA Receptors on Insulin Producing Cells in the Brain of Drosophila. PLoS ONE 5(12): e15780. (Export to RIS)
FlyBase ID	FBrf0212696
Publication Type	Research paper
PubMed ID	21209905
PubMed Abstract	Insulin-like peptides (ILPs) regulate growth, reproduction, metabolic homeostasis, life span and stress resistance in worms, flies and mammals. A set of insulin producing cells (IPCs) in the Drosophila brain that express three ILPs (DILP2, 3 and 5) have been the main focus of interest in hormonal DILP signaling. Little is, however, known about factors that regulate DILP production and release by these IPCs. Here we show that the IPCs express the metabotropic GABA(B) receptor (GBR), but not the ionotropic GABA(A) receptor subunit RDL. Diminishing the GBR expression on these cells by targeted RNA interference abbreviates life span, decreases metabolic stress resistance and alters carbohydrate and lipid metabolism at stress, but not growth in Drosophila. A direct effect of diminishing GBR on IPCs is an increase in DILP immunofluorescence in these cells, an effect that is accentuated at starvation. Knockdown of irk3, possibly part of a G protein-activated inwardly rectifying K(+) channel that may link to GBRs, phenocopies GBR knockdown in starvation experiments. Our experiments suggest that the GBR is involved in inhibitory control of DILP production and release in adult flies at metabolic stress and that this receptor mediates a GABA signal from brain interneurons that may convey nutritional signals. This is the first demonstration of a neurotransmitter that inhibits insulin signaling in its regulation of metabolism, stress and life span in an invertebrate brain.
DOI	10.1371/journal.pone.0015780
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	PLoS ONE
Title	PLoS ONE
Publication Year	2006-
ISBN/ISSN	1932-6203
Data from Reference
Alleles (17)
	Avic\GFP^{S65T.Scer\UAS} Dcr-2^Scer\UAS.cDa GABA-B-R2^{dsRNA.Scer\UAS} GABA-B-R2^KK100020 Ilp2^Scer\UAS.cBa Irk3^GD1764 Irk3^KK107031 Mmus\Cd8a^{Scer\UAS.T:Avic\GFP} Rdl^{dsRNA.4-5.Scer\UAS} Scer\GAL4^ey-OK107 Scer\GAL4^GABA-B-R2.PR Scer\GAL4^Gad1.3.098 Scer\GAL4^Gad1.PS Scer\GAL4^Ilp2.PW Scer\GAL4^Ilp3.PB Scer\GAL4^Mef2.247 Scer\GAL4^Rdl.PS
Constructs (16)
	P{GABA-B-R2-GAL4.R} P{Gad1-GAL4.3.098} P{Gad1-GAL4.S} P{GD1764} P{Ilp2-GAL4.W} P{Ilp3-Gal4.B} P{KK100020} P{KK107031} P{Mef2-GAL4.247} P{Rdl-GAL4.S} P{UAS-Dcr-2.D} P{UAS-GABA-B-R2.RNAi} P{UAS-GFP.S65T} P{UAS-Ilp2.B} P{UAS-mCD8::GFP.L} P{UAS-Rdl.RNAi.4-5}
Genes (9)
	Avic\GFP Dcr-2 GABA-B-R2 Gad1 Ilp2 Irk3 Mmus\Cd8a Rdl Scer\GAL4
Insertions (1)
	P{GawB}ey^OK107
Natural transposons (1)
	P-element
Transcripts (4)
	Scer\GAL4^ey-OK107RA Scer\GAL4^GABA-B-R2.PRRA Scer\GAL4^Ilp2.PWRA Scer\GAL4^Rdl.PSRA