Dataset Information

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

ABSTRACT: The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system.

SUBMITTER: Talsma AD

PROVIDER: S-EPMC3409758 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

Talsma Aaron D AD Christov Christo P CP Terriente-Felix Ana A Linneweber Gerit A GA Perea Daniel D Wayland Matthew M Shafer Orie T OT Miguel-Aliaga Irene I

Proceedings of the National Academy of Sciences of the United States of America 20120709 30

The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in Drosophila is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling ...[more]

PMID: 22778427

Similar Datasets

Project description:Pigment-dispersing factor neuropeptides (PDFs) occur in a wide range of protostomes including ecdysozoans (= molting animals) and lophotrochozoans (mollusks, annelids, flatworms, and allies). Studies in insects revealed that PDFs play a role as coupling factors of circadian pacemaker cells, thereby controlling rest-activity rhythms. While the last common ancestor of protostomes most likely possessed only one pdf gene, two pdf homologs, pdf-I and pdf-II, might have been present in the last common ancestors of Ecdysozoa and Panarthropoda (Onychophora + Tardigrada + Arthropoda). One of these homologs, however, was subsequently lost in the tardigrade and arthropod lineages followed by independent duplications of pdf-I in tardigrades and decapod crustaceans. Due to the ancestral set of two pdf genes, the study of PDFs and their receptor (PDFR) in Onychophora might reveal the ancient organization and function of the PDF/PDFR system in panarthropods. Therefore, we deorphanized the PDF receptor and generated specific antibodies to localize the two PDF peptides and their receptor in the onychophoran Euperipatoides rowelli. We further conducted bioluminescence resonance energy transfer (BRET) experiments on cultured human cells (HEK293T) using an Epac-based sensor (Epac-L) to examine cAMP responses in transfected cells and to reveal potential differences in the interaction of PDF-I and PDF-II with PDFR from E. rowelli. These data show that PDF-II has a tenfold higher potency than PDF-I as an activating ligand. Double immunolabeling revealed that both peptides are co-expressed in E. rowelli but their respective levels of expression differ between specific cells: some neurons express the same amount of both peptides, while others exhibit higher levels of either PDF-I or PDF-II. The detection of the onychophoran PDF receptor in cells that additionally express the two PDF peptides suggests autoreception, whereas spatial separation of PDFR- and PDF-expressing cells supports hormonal release of PDF into the hemolymph. This suggests a dual role of PDF peptides-as hormones and as neurotransmitters/neuromodulators-in Onychophora.

Project description:Behavior and physiology are orchestrated by neuropeptides acting as central neuromodulators and circulating hormones. An outstanding question is how these neuropeptides function to coordinate complex and competing behaviors. In Drosophila, the neuropeptide leucokinin (LK) modulates diverse functions, but mechanisms underlying these complex interactions remain poorly understood. As a first step towards understanding these mechanisms, we delineated LK circuitry that governs various aspects of post-feeding physiology and behavior. We found that impaired LK signaling in Lk and Lk receptor (Lkr) mutants affects diverse but coordinated processes, including regulation of stress, water homeostasis, feeding, locomotor activity, and metabolic rate. Next, we sought to define the populations of LK neurons that contribute to the different aspects of this physiology. We find that the calcium activity in abdominal ganglia LK neurons (ABLKs), but not in the two sets of brain neurons, increases specifically following water consumption, suggesting that ABLKs regulate water homeostasis and its associated physiology. To identify targets of LK peptide, we mapped the distribution of Lkr expression, mined a brain single-cell transcriptome dataset for genes coexpressed with Lkr, and identified synaptic partners of LK neurons. Lkr expression in the brain insulin-producing cells (IPCs), gut, renal tubules and chemosensory cells, correlates well with regulatory roles detected in the Lk and Lkr mutants. Furthermore, these mutants and flies with targeted knockdown of Lkr in IPCs displayed altered expression of insulin-like peptides (DILPs) and transcripts in IPCs and increased starvation resistance. Thus, some effects of LK signaling appear to occur via DILP action. Collectively, our data suggest that the three sets of LK neurons have different targets, but modulate the establishment of post-prandial homeostasis by regulating distinct physiological processes and behaviors such as diuresis, metabolism, organismal activity and insulin signaling. These findings provide a platform for investigating feeding-related neuroendocrine regulation of vital behavior and physiology.

Dataset Information

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

Publications

Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets