| 1. |
- Birse, Ryan T., et al.
(author)
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Regulation of insulin-producing cells in the adult Drosophila brain via the tachykinin peptide receptor DTKR
- 2011
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In: Journal of Experimental Biology. - : The Company of Biologists. - 0022-0949 .- 1477-9145. ; 214, s. 4201-4208
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Journal article (peer-reviewed)abstract
- Drosophila insulin-like peptides (DILPs) play important hormonal roles in the regulation of metabolic carbohydrates and lipids, but also in reproduction, growth, stress resistance and aging. In spite of intense studies of insulin signaling in Drosophilag the regulation of DILP production and release in adult fruit flies is poorly understood. Here we investigated the role of Drosophila tachykinin-related peptides (DTKs) and their receptors, DTKR and NKD, in the regulation of brain insulin-producing cells (IPCs) and aspects of DILP signaling. First, we show DTK-immunoreactive axon terminations close to the presumed dendrites of the IPCs, and DTKR immunolabeling in these cells. Second, we utilized targeted RNA interference to knock down expression of the DTK receptor, DTKR, in IPCs and monitored the effects on Dilp transcript levels in the brains of fed and starved flies. Dilp2 and Dilp3, but not Dilp5, transcripts were significantly affected by DTKR knockdown in IPCs, both in fed and starved flies. Both Dilp2 and Dilp3 transcripts increased in fed flies with DTKR diminished in IPCs whereas at starvation the Dilp3 transcript plummeted and Dilp2 increased. We also measured trehalose and lipid levels as well as survival in transgene flies at starvation. Knockdown of DTKR in IPCs leads to increased lifespan and a faster decrease of trehalose at starvation but has no significant effect on lipid levels. Finally, we targeted the IPCs with RNAi or ectopic expression of the other DTK receptor, NKD, but found no effect on survival at starvation. Our results suggest that DTK signaling, via DTKR, regulates the brain IPCs.
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| 2. |
- Ignell, Rickard, et al.
(author)
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Presynaptic peptidergic modulation of olfactory receptor neurons in Drosophila.
- 2009
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:31, s. 13070-13075
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Journal article (peer-reviewed)abstract
- The role of classical neurotransmitters in the transfer and processing of olfactory information is well established in many organisms. Neuropeptide action, however, is largely unexplored in any peripheral olfactory system. A subpopulation of local interneurons (LNs) in the Drosophila antannal lobe is peptidergic, expressing Drosophila tachykinins (DTKs). We show here that olfactory receptor neurons (ORNs) express the DTK receptor (DTKR). Using two-photon microscopy, we found that DTK applied to the antennal lobe suppresses presynaptic calcium and synaptic transmission in the ORNs. Furthermore, reduction of DTKR expression in ORNs by targeted RNA interference eliminates presynaptic suppression and alters olfactory behaviors. We detect opposite behavioral phenotypes after reduction and over expression of DTKR in ORNs. Our findings suggest a presynaptic inhibitory feedback to ORNs from peptidergic LNs in the antennal lobe.
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| 3. |
- Poels, Jeroen, et al.
(author)
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Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6.
- 2009
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In: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:3, s. 545-56
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Journal article (peer-reviewed)abstract
- Neuropeptides related to vertebrate tachykinins have been identified in Drosophila and are referred to as drosotachykinins, or DTKs. Two Drosophila G protein-coupled receptors, designated NKD (neurokinin receptor from Drosophila; CG6515) and DTKR (Drosophila tachykinin receptor; CG7887), display sequence similarities to mammalian tachykinin receptors. Whereas DTKR was shown to be activated by DTKs [Birse RT, Johnson EC, Taghert PH, Nässel DR. Widely distributed Drosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides. J Neurobiol 2006;66:33-46; Poels J, Verlinden H, Fichna J, Van Loy T, Franssens V, Studzian K, et al. Functional comparison of two evolutionary conserved insect neurokinin-like receptors. Peptides 2007;28:103-8] and was localized by immunocytochemistry in Drosophila central nervous system (CNS), agonist-dependent activation and distribution of NKD have not yet been investigated in depth. In the present study, we have challenged NKD-expressing mammalian and insect cells with a library of Drosophila neuropeptides and discovered DTK-6 as a specific agonist that can induce a calcium response in these cells. In addition, we have produced antisera to sequences from NKD protein to analyze receptor distribution. We found that NKD is less abundantly distributed in the central nervous system than DTKR, and only NKD was found in the intestine. In fact, the two receptors are distributed in mutually exclusive patterns in the CNS. The combined distribution of the receptors in brain neuropils corresponds well with the distribution of DTKs. Most interestingly, NKD appears to be activated only by DTK-6, known to possess an Ala-substitution in an otherwise conserved C-terminal core motif. Our findings suggest that NKD and DTKR provide substrates for two functionally and spatially separated peptide signaling systems.
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| 4. |
- Söderberg, Jeannette A.E. 1983-, et al.
(author)
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Insulin Production and Signaling in Renal Tubules of Drosophila is under Control of Tachykinin-related Peptide and Regulates Stress Resistance
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:5, s. e19866-
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Journal article (peer-reviewed)abstract
- The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolichomeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of whichare produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renaltubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but alsoplay roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules byDrosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells.Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted inincreased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus,stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations ofS6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locallyon tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in therenal tubules and that this signaling is under control of stress-induced release of peptide hormone.
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