Gene Symbol: Pdfr
Description: Pigment-dispersing factor receptor
Alias: BACR25B3.3, CG13758, DmeCG13758, Dmel\CG13758, EG:BACR25B3.3, Han, PDF-R1, PDFR, Pdf-R1, PdfR, anon-WO0170980.157, anon-WO0170980.158, gop, han, pdfr, Pigment-dispersing factor receptor, CG13758-PA, CG13758-PB, CG13758-PC, CG13758-PD, PDF receptor, PDF-receptor, Pdf recep- tor, Pdfr-PA, Pdfr-PB, Pdfr-PC, Pdfr-PD, groom-of-pdf, pigment dispersing factor receptor, pigment dispersing factor receptor 1, pigment-dispersing factor receptor
Species: fruit fly

Top Publications

  1. Mertens I, Vandingenen A, Johnson E, Shafer O, Li W, Trigg J, et al. PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. Neuron. 2005;48:213-9 pubmed
    ..In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells...
  2. Im S, Taghert P. PDF receptor expression reveals direct interactions between circadian oscillators in Drosophila. J Comp Neurol. 2010;518:1925-45 pubmed publisher
    ..to numerous aspects of behavioral and molecular rhythms, determining precisely where and how signaling via the PDF receptor (PDFR) occurs is now a central question in the field...
  3. Yao Z, Macara A, Lelito K, Minosyan T, Shafer O. Analysis of functional neuronal connectivity in the Drosophila brain. J Neurophysiol. 2012;108:684-96 pubmed publisher
    ..Furthermore, the effectiveness of this approach in the fly brain suggests that similar methods using appropriate heterologous receptors might be adopted for other widely used model systems. ..
  4. Lear B, Zhang L, Allada R. The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior. PLoS Biol. 2009;7:e1000154 pubmed publisher
    ..Using circuit-directed rescue of PDF receptor mutants, we show that PDF targeting of just approximately 30 non-PDF evening circadian neurons is sufficient to ..
  5. Duvall L, Taghert P. The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila. PLoS Biol. 2012;10:e1001337 pubmed publisher
    ..The PDF receptor (PDF-R) is present in both M and subsets of E cells...
  6. Im S, Li W, Taghert P. PDFR and CRY signaling converge in a subset of clock neurons to modulate the amplitude and phase of circadian behavior in Drosophila. PLoS ONE. 2011;6:e18974 pubmed publisher
    ..We report that the neuropeptide PDF receptor and the circadian photoreceptor CRYPTOCROME (CRY) are precisely co-expressed in a subset of pacemakers, and ..
  7. Shafer O, Kim D, Dunbar Yaffe R, Nikolaev V, Lohse M, Taghert P. Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging. Neuron. 2008;58:223-37 pubmed publisher
    ..neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing ..
  8. Cusumano P, Klarsfeld A, Chélot E, Picot M, Richier B, Rouyer F. PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila. Nat Neurosci. 2009;12:1431-7 pubmed publisher
    ..cycling and the presence of evening activity relied on PDF secretion from the large ventral lateral neurons and PDF receptor function in the LN-EO...
  9. Zhang L, Chung B, Lear B, Kilman V, Liu Y, Mahesh G, et al. DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila. Curr Biol. 2010;20:591-9 pubmed publisher
    ..The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions. Flies also respond to the onset of light and dark with acute increases in activity...

More Information


  1. Harmar A. Family-B G-protein-coupled receptors. Genome Biol. 2001;2:REVIEWS3013 pubmed
    ..In this article, I describe the structures and functions of family-B GPCRs and propose a simplified nomenclature for these proteins. ..
  2. Talsma A, Christov C, Terriente Félix A, Linneweber G, Perea D, Wayland M, et al. Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in Drosophila. Proc Natl Acad Sci U S A. 2012;109:12177-82 pubmed publisher
    ..We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-..
  3. Kula Eversole E, Nagoshi E, Shang Y, Rodriguez J, Allada R, Rosbash M. Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila. Proc Natl Acad Sci U S A. 2010;107:13497-502 pubmed publisher
    ..The results suggest that RNA cycling is much more prominent in circadian neurons than elsewhere in heads and may be particularly important for the functioning of these neurons. ..
  4. Parisky K, Agosto J, Pulver S, Shang Y, Kuklin E, Hodge J, et al. PDF cells are a GABA-responsive wake-promoting component of the Drosophila sleep circuit. Neuron. 2008;60:672-82 pubmed publisher
  5. Choi C, Cao G, Tanenhaus A, McCarthy E, Jung M, Schleyer W, et al. Autoreceptor control of peptide/neurotransmitter corelease from PDF neurons determines allocation of circadian activity in drosophila. Cell Rep. 2012;2:332-44 pubmed publisher
    ..Previous studies have demonstrated the requirement for PDF signaling to PDF receptor (PDFR)-expressing dorsal clock neurons in organizing circadian activity...
  6. Hyun S, Lee Y, Hong S, Bang S, Paik D, Kang J, et al. Drosophila GPCR Han is a receptor for the circadian clock neuropeptide PDF. Neuron. 2005;48:267-78 pubmed
    ..Therefore, we herein propose that Han is a PDF receptor regulating circadian behavioral rhythm through coordination of activities of clock neurons.
  7. Gorostiza E, Ceriani M. Retrograde bone morphogenetic protein signaling shapes a key circadian pacemaker circuit. J Neurosci. 2013;33:687-96 pubmed publisher
    ..show that mature sLNv circuits require PDF signaling during early development, acting through its cognate receptor PDFR at postsynaptic targets...
  8. Zhang Y, Emery P. GW182 controls Drosophila circadian behavior and PDF-receptor signaling. Neuron. 2013;78:152-65 pubmed publisher
    ..Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function...
  9. Cardoso J, Pinto V, Vieira F, Clark M, Power D. Evolution of secretin family GPCR members in the metazoa. BMC Evol Biol. 2006;6:108 pubmed
    ..In this study a comprehensive description of family 2 GPCR evolution is given based on in silico and expression analyses of the invertebrate receptor genes...
  10. Yao Z, Shafer O. The Drosophila circadian clock is a variably coupled network of multiple peptidergic units. Science. 2014;343:1516-20 pubmed publisher
    ..Our work reveals that the circadian clock neuron network is not orchestrated by a small group of master pacemakers but rather consists of multiple independent oscillators, each of which drives rhythms in activity. ..
  11. Krupp J, Billeter J, Wong A, Choi C, Nitabach M, Levine J. Pigment-dispersing factor modulates pheromone production in clock cells that influence mating in drosophila. Neuron. 2013;79:54-68 pubmed publisher
    ..Our findings highlight the role of neuropeptide signaling and the circadian system in synchronizing the physiological and behavioral processes that govern social interactions. ..
  12. Wülbeck C, Grieshaber E, Helfrich Forster C. Blocking endocytosis in Drosophila's circadian pacemaker neurons interferes with the endogenous clock in a PDF-dependent way. Chronobiol Int. 2009;26:1307-22 pubmed publisher
    ..This effect was absent in PDF receptor null mutants, indicating that we interfered with PDF receptor-mediated endocytosis...
  13. Chung B, Kilman V, Keath J, Pitman J, Allada R. The GABA(A) receptor RDL acts in peptidergic PDF neurons to promote sleep in Drosophila. Curr Biol. 2009;19:386-90 pubmed publisher
    ..In addition, RDL is detectable most strongly on the large subset of PDF+ pacemaker neurons. These results suggest that GABAergic inhibition of arousal-promoting PDF neurons is an important mode of sleep-wake regulation in vivo. ..
  14. Lear B, Merrill C, Lin J, Schroeder A, Zhang L, Allada R. A G protein-coupled receptor, groom-of-PDF, is required for PDF neuron action in circadian behavior. Neuron. 2005;48:221-7 pubmed
    ..gop is expressed most strongly in the dorsal brain in regions that lie in proximity to PDF-containing nerve terminals. Taken together, these studies implicate GOP as a PDF receptor in Drosophila.
  15. Picot M, Klarsfeld A, Chélot E, Malpel S, Rouyer F. A role for blind DN2 clock neurons in temperature entrainment of the Drosophila larval brain. J Neurosci. 2009;29:8312-20 pubmed publisher
    ..in LD depends on the pigment-dispersing factor (PDF) neuropeptide in four lateral neurons (LNs), and on the PDF receptor in the DN2s...
  16. Li C, Chen M, Sang M, Liu X, Wu W, Li B. Comparative genomic analysis and evolution of family-B G protein-coupled receptors from six model insect species. Gene. 2013;519:1-12 pubmed publisher
    ..On the other hand, this study provides us with multiple function of GPCR-Bs in differential organisms, which will be also the potential attacking targets for new pesticides and drugs. ..
  17. Zhang L, Lear B, Seluzicki A, Allada R. The CRYPTOCHROME photoreceptor gates PDF neuropeptide signaling to set circadian network hierarchy in Drosophila. Curr Biol. 2009;19:2050-5 pubmed publisher
    ..To examine the role of PDF in light-dark conditions, we examined flies lacking both the PDF receptor (PDFR) and the circadian photoreceptor CRYPTOCHROME (CRY)...
  18. Seluzicki A, Flourakis M, Kula Eversole E, Zhang L, Kilman V, Allada R. Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior. PLoS Biol. 2014;12:e1001810 pubmed publisher
    ..kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons...
  19. Guo F, Cerullo I, Chen X, Rosbash M. PDF neuron firing phase-shifts key circadian activity neurons in Drosophila. elife. 2014;3: pubmed publisher
    ..different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons...
  20. Agrawal T, Sadaf S, Hasan G. A genetic RNAi screen for IP?/Ca²? coupled GPCRs in Drosophila identifies the PdfR as a regulator of insect flight. PLoS Genet. 2013;9:e1003849 pubmed publisher
    ..Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight...
  21. Choi C, Fortin J, McCarthy E, Oksman L, Kopin A, Nitabach M. Cellular dissection of circadian peptide signals with genetically encoded membrane-tethered ligands. Curr Biol. 2009;19:1167-75 pubmed publisher
    ..melanogaster, rhythmic secretion of the neuropeptide pigment-dispersing factor (PDF) and activation of its GPCR (PDFR) are important for intercellular communication of phase information and coordination of clock neuron oscillation...
  22. Kaneko H, Head L, Ling J, Tang X, Liu Y, Hardin P, et al. Circadian rhythm of temperature preference and its neural control in Drosophila. Curr Biol. 2012;22:1851-7 pubmed publisher
  23. Cardoso J, Félix R, Power D. Nematode and arthropod genomes provide new insights into the evolution of class 2 B1 GPCRs. PLoS ONE. 2014;9:e92220 pubmed publisher
  24. Kunst M, Hughes M, Raccuglia D, Felix M, Li M, Barnett G, et al. Calcitonin gene-related peptide neurons mediate sleep-specific circadian output in Drosophila. Curr Biol. 2014;24:2652-64 pubmed publisher
    ..Our results indicate that outputs of the clock controlling sleep and locomotor rhythms are mediated via distinct neuronal pathways. ..
  25. Shafer O, Yao Z. Pigment-Dispersing Factor Signaling and Circadian Rhythms in Insect Locomotor Activity. Curr Opin Insect Sci. 2014;1:73-80 pubmed
  26. Liu S, Lamaze A, Liu Q, Tabuchi M, Yang Y, Fowler M, et al. WIDE AWAKE mediates the circadian timing of sleep onset. Neuron. 2014;82:151-66 pubmed publisher
    ..We propose that WAKE acts as a clock output molecule specifically for sleep, inhibiting LNvs at dusk to promote the transition from wake to sleep. ..
  27. Linneweber G, Jacobson J, Busch K, Hudry B, Christov C, Dormann D, et al. Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching. Cell. 2014;156:69-83 pubmed publisher
    ..Thus, we describe a novel mechanism by which nutritional cues modulate neuronal activity to give rise to organ-specific, long-lasting changes in vascular architecture. ..
  28. Means J, Venkatesan A, Gerdes B, Fan J, Bjes E, Price J. Drosophila spaghetti and doubletime link the circadian clock and light to caspases, apoptosis and tauopathy. PLoS Genet. 2015;11:e1005171 pubmed publisher
    ..They establish a link between the circadian clock factors, light, cell death pathways and Tau toxicity, potentially via dysregulation of circadian neuronal remodeling in the optic lobes. ..
  29. Bendena W, Campbell J, Zara L, Tobe S, Chin Sang I. Select Neuropeptides and their G-Protein Coupled Receptors in Caenorhabditis Elegans and Drosophila Melanogaster. Front Endocrinol (Lausanne). 2012;3:93 pubmed publisher
    ..melanogaster and C. elegans and the behaviors that have been uncovered through genetic manipulation. ..
  30. Zheng X, Sowcik M, Chen D, Sehgal A. Casein kinase 1 promotes synchrony of the circadian clock network. Mol Cell Biol. 2014;34:2682-94 pubmed
    ..These data thus demonstrate that overall reduction of DBT causes long and arrhythmic behavior, and they reveal an unexpected role of DBT in promoting synchrony of the circadian clock network. ..
  31. Kemppainen E, Fernández Ayala D, Galbraith L, O Dell K, Jacobs H. Phenotypic suppression of the Drosophila mitochondrial disease-like mutant tko(25t) by duplication of the mutant gene in its natural chromosomal context. Mitochondrion. 2009;9:353-63 pubmed publisher
    ..Increased mutant gene dosage can thus compensate the mutant phenotype, but only when located in its normal chromosomal context. ..
  32. Isaac R, Johnson E, Audsley N, Shirras A. Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila. J Exp Biol. 2007;210:4465-70 pubmed
    ..fragments were able to increase intracellular cAMP levels in HEK293 cells cotransfected with the Drosophila PDF receptor cDNA and a firefly luciferase reporter gene, confirming that such cleavage results in PDF inactivation...
  33. Holmes T, Sheeba V. Circadian pathway: the other shoe drops. Curr Biol. 2005;15:R987-9 pubmed
    ..The discovery of the PDF receptor heralds progress in understanding the circadian pacemaker circuit and output pathways in insects.
  34. Luo W, Sehgal A. Regulation of circadian behavioral output via a MicroRNA-JAK/STAT circuit. Cell. 2012;148:765-79 pubmed publisher
    ..In addition, central clock neurons project in the vicinity of Upd-expressing neurons, providing a possible physical connection by which the central clock could regulate JAK/STAT signaling to control rest:activity rhythms. ..
  35. Beckwith E, Lelito K, Hsu Y, Medina B, SHAFER O, Ceriani M, et al. Functional conservation of clock output signaling between flies and intertidal crabs. J Biol Rhythms. 2011;26:518-29 pubmed publisher
    ..brains shows that PDF and ?-PDH-I are equally effective in inducing the signal transduction cascade of the PDF receptor, but ?-PDH-II fails to induce a normal cascade...
  36. Collins B, Kaplan H, Cavey M, Lelito K, Bahle A, Zhu Z, et al. Differentially timed extracellular signals synchronize pacemaker neuron clocks. PLoS Biol. 2014;12:e1001959 pubmed publisher
    ..Unexpectedly, we found that the PDF Receptor (PdfR) is required in both LNvs and DN1s to maintain synchronized LNv clocks...
  37. Vecsey C, P rez N, Griffith L. The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons. J Neurophysiol. 2014;111:1033-45 pubmed publisher
    ..PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability...
  38. Pirooznia S, Chiu K, Chan M, Zimmerman J, Elefant F. Epigenetic regulation of axonal growth of Drosophila pacemaker cells by histone acetyltransferase tip60 controls sleep. Genetics. 2012;192:1327-45 pubmed publisher
  39. Kunst M, Tso M, Ghosh D, Herzog E, Nitabach M. Rhythmic control of activity and sleep by class B1 GPCRs. Crit Rev Biochem Mol Biol. 2015;50:18-30 pubmed publisher
    ..molecular mechanisms by which class B1 GPCRs, especially the mammalian VPAC2 receptor and its functional homologue PDFR in Drosophila and C. elegans, regulate arousal and daily rhythms of sleep and wake...
  40. Norgate M, Southon A, Zou S, Zhan M, Sun Y, Batterham P, et al. Copper homeostasis gene discovery in Drosophila melanogaster. Biometals. 2007;20:683-97 pubmed
    ..Building on this information, there is great potential for the further use of Drosophila for copper homeostasis gene discovery. ..
  41. Liang X, Holy T, Taghert P. Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo. Science. 2016;351:976-81 pubmed publisher
    ..Loss of the receptor for the neuropeptide PDF promoted synchrony of Ca(2+) waves. Thus, neuropeptide modulation is required to sequentially time outputs from a network of synchronous molecular pacemakers. ..
  42. Fernández M, Chu J, Villella A, Atkinson N, Kay S, Ceriani M. Impaired clock output by altered connectivity in the circadian network. Proc Natl Acad Sci U S A. 2007;104:5650-5 pubmed
    ..Our observations demonstrate that subtle structural changes within the circadian network are responsible for behavioral arrhythmicity. ..
  43. Goda T, Tang X, Umezaki Y, Chu M, Kunst M, Nitabach M, et al. Drosophila DH31 Neuropeptide and PDF Receptor Regulate Night-Onset Temperature Preference. J Neurosci. 2016;36:11739-11754 pubmed
    ..Here, we demonstrate that the neuropeptide diuretic hormone 31 (DH31) and pigment-dispersing factor receptor (PDFR) contribute to regulate the preferred temperature decrease at night-onset...
  44. Klose M, Duvall L, Li W, Liang X, Ren C, Steinbach J, et al. Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation. Neuron. 2016;90:781-794 pubmed publisher
    ..Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. ..
  45. Damulewicz M, Loboda A, Bukowska Strakova K, Jozkowicz A, Dulak J, Pyza E. Clock and clock-controlled genes are differently expressed in the retina, lamina and in selected cells of the visual system of Drosophila melanogaster. Front Cell Neurosci. 2015;9:353 pubmed publisher
    ..of the following clock genes; per, tim, clk, and cry and clock-controlled genes (ccgs); Atpα, nrv2, brp, Pdfr. We found that the expression of gene studied is specific for the retina and lamina...
  46. Head L, Tang X, Hayley S, Goda T, Umezaki Y, Chang E, et al. The influence of light on temperature preference in Drosophila. Curr Biol. 2015;25:1063-8 pubmed publisher
    ..that the circadian clock neurons posterior dorsal neurons 1 (DN1(p)s) and Pigment-Dispersing Factor Receptor (PDFR) play a role in LDTP...
  47. Duvall L, Taghert P. E and M circadian pacemaker neurons use different PDF receptor signalosome components in drosophila. J Biol Rhythms. 2013;28:239-48 pubmed publisher
    ..b>PDF receptor (PDF-R) is expressed by both M (sLNv) and E (LNd) pacemaker subclasses and is coupled to G(s?) in both cases...
  48. Kim W, Jan L, Jan Y. A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating. Neuron. 2013;80:1190-205 pubmed publisher
    ..LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the ..