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Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.
Stockholm University, Faculty of Science, Department of Zoology, Functional Morphology.ORCID iD: 0000-0002-1147-7766
2012 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 69, no 23, 4051-4066 p.Article in journal (Refereed) Published
Abstract [en]

Insulin/IGF-like signaling regulates the development, growth, fecundity, metabolic homeostasis, stress resistance and lifespan in worms, flies and mammals. Eight insulin-like peptides (DILP1-8) are found in Drosophila. Three of these (DILP2, 3 and 5) are produced by a set of median neurosecretory cells (insulin-producing cells, IPCs) in the brain. Activity in the IPCs of adult flies is regulated by glucose and several neurotransmitters and neuropeptides. One of these, short neuropeptide F (sNPF), regulates food intake, growth and Dilp transcript levels in IPCs via the sNPF receptor (sNPFR1) expressed on IPCs. Here we identify a set of brain neurons that utilizes sNPF to activate the IPCs. These sNPF-expressing neurons (dorsal lateral peptidergic neurons, DLPs) also produce the neuropeptide corazonin (CRZ) and have axon terminations impinging on IPCs. Knockdown of either sNPF or CRZ in DLPs extends survival in flies exposed to starvation and alters carbohydrate and lipid metabolism. Expression of sNPF in DLPs in the sNPF mutant background is sufficient to rescue wild-type metabolism and response to starvation. Since CRZ receptor RNAi in IPCs affects starvation resistance and metabolism, similar to peptide knockdown in DLPs, it is likely that also CRZ targets the IPCs. Knockdown of sNPF, but not CRZ in DLPs decreases transcription of Dilp2 and 5 in the brain, suggesting different mechanisms of action on IPCs of the two co-released peptides. Our findings indicate that sNPF and CRZ co-released from a small set of neurons regulate IPCs, stress resistance and metabolism in adult Drosophila.

Place, publisher, year, edition, pages
2012. Vol. 69, no 23, 4051-4066 p.
Keyword [en]
Insulin signaling, Peptide hormones, Neuropeptides, Drosophila melanogaster
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:su:diva-80362DOI: 10.1007/s00018-012-1097-zISI: 000310868200015PubMedID: 22828865OAI: oai:DiVA.org:su-80362DiVA: diva2:553256
Funder
Swedish Research Council
Available from: 2012-09-18 Created: 2012-09-18 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Regulation of insulin producing cells, stress responses and metabolism in Drosophila
Open this publication in new window or tab >>Regulation of insulin producing cells, stress responses and metabolism in Drosophila
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Drosophila, neuropeptides have regulatory roles in development, growth, metabolism and reproduction. This study focused on GABA and the neuropeptides Drosophila tachykinin (DTK), short neuropeptide F (sNPF), adipokinetic hormone (AKH), corazonin (CRZ) and Drosophila insulin-like peptides (DILPs) as possible regulators of metabolic stress responses and homeostasis. We showed that metabotropic GABAB receptors (GBRs) are expressed on brain insulin producing cells (IPCs), suggesting an inhibitory regulation of these cells by GABA. Knockdown of GBR on IPCs shortened lifespan and stress resistance, altered carbohydrate and lipid metabolism at stress (paper I). We showed that three different neuropeptides; DTK, sNPF and ITP, are co-expressed in five pairs of adult neurosecretory cells (paper II). ITP-knock down was not studied yet, but sNPF- and DTK-knock down flies showed decreased stress resistance at desiccation and starvation and decreased water levels at desiccation, suggesting that these peptides are involved in water homeostasis during stress conditions. sNPF was previously shown to affect feeding, growth and DILP expression via the IPCs, but it was not known which sNPF-expressing neurons are responsible for these actions. We could identify a specific set of bilateral neurons (DLPs) that co-express sNPF and corazonin that target the IPCs. We showed that these peptides co-released from DLPs regulate DILP transcription and probably release in the adult Drosophila brain and thus have roles in regulation of stress resistance and metabolism (paper III). AKH signaling was previously shown to affect hemolymph carbohydrate levels and lipid stores in Drosophila. Insulin (DILP) signaling and AKH signaling are suggested to have opposing effects on lipid and sugar metabolism in Drosophila. We studied the possible functional relationship between these two systems; do they mutually regulate each other?  Our results suggest action of DILPs via the Insulin Receptor on the IPCs and the AKH producing cells, but we could not provide evidence for AKH action on IPCs or AKH cells (paper IV). 

Place, publisher, year, edition, pages
Stockholm, Sweden: Department of Zoology, Stockholm Univeristy, 2012. 33 p.
Keyword
Insulin signaling, Drosophila melanogaster, peptide hormones, neuropeptides, GABA
National Category
Cell Biology
Research subject
Functional Zoomorphology
Identifiers
urn:nbn:se:su:diva-80518 (URN)978-91-7447-582-1 (ISBN)
Public defence
2012-10-26, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Opponent
Supervisors
Funder
Swedish Research Council
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Epub ahead of print. Paper 4: Manuscript.

Available from: 2012-10-04 Created: 2012-09-24 Last updated: 2014-10-28Bibliographically approved

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