A G Protein-Coupled Receptor, groom-of-PDF, Is Required for PDF Neuron Action in Circadian Behavior

The neuropeptide Pigment-Dispersing Factor (PDF) plays a critical role in mediating circadian control of behavior in Drosophila. Here we identify mutants (groom-of-PDF; gop) that display phase-advanced evening activity and poor free-running rhythmicity, phenocopying pdf mutants. In gop mutants, a spontaneous retrotransposon disrupts a coding exon of a G protein-coupled receptor, CG13758. Disruption of the receptor is accompanied by phase-advanced oscillations of the core clock protein PERIOD. Moreover, effects on circadian timing induced by perturbation of PDF neurons require gop. Yet PDF oscillations themselves remain robust in gop mutants, suggesting that GOP acts downstream of PDF. 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.

[1]  P. Taghert,et al.  PDF Receptor Signaling in Drosophila Contributes to Both Circadian and Geotactic Behaviors , 2005, Neuron.

[2]  Jeffrey C. Hall,et al.  Drosophila Free-Running Rhythms Require Intercellular Communication , 2003, PLoS biology.

[3]  A. Sehgal,et al.  Why a fly? Using Drosophila to understand the genetics of circadian rhythms and sleep. , 2004, Sleep.

[4]  B. H. Miller,et al.  Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock , 2002, Cell.

[5]  R. Drysdale,et al.  Molecular characterization of eag: a gene affecting potassium channels in Drosophila melanogaster. , 1991, Genetics.

[6]  E. Maywood,et al.  The VPAC2 Receptor Is Essential for Circadian Function in the Mouse Suprachiasmatic Nuclei , 2002, Cell.

[7]  Kevin P. Keegan,et al.  A role for casein kinase 2alpha in the Drosophila circadian clock. , 2002, Nature.

[8]  Charlotte Helfrich-Förster,et al.  The neuroarchitecture of the circadian clock in the brain of Drosophila melanogaster , 2003, Microscopy research and technique.

[9]  A. Sehgal,et al.  A Circadian Output in Drosophila Mediated by Neurofibromatosis-1 and Ras/MAPK , 2001, Science.

[10]  I. Levitan,et al.  Pattern of distribution and cycling of SLOB, Slowpoke channel binding protein, in Drosophila , 2004, BMC Neuroscience.

[11]  Jeffrey C. Hall,et al.  Neuroanatomy of cells expressing clock genes in Drosophila: Transgenic manipulation of the period and timeless genes to mark the perikarya of circadian pacemaker neurons and their projections , 2000, The Journal of comparative neurology.

[12]  A. Klarsfeld,et al.  Novel Features of Cryptochrome-Mediated Photoreception in the Brain Circadian Clock of Drosophila , 2004, The Journal of Neuroscience.

[13]  Kevin P. Keegan,et al.  A role for casein kinase 2α in the Drosophila circadian clock , 2002, Nature.

[14]  G. Stormo,et al.  The Neuropeptide Pigment-Dispersing Factor Coordinates Pacemaker Interactions in the Drosophila Circadian System , 2004, The Journal of Neuroscience.

[15]  Jeffrey C. Hall,et al.  A pdf neuropeptide gene mutation and ablation of PDF neurons each cause severe abnormalities of behavioral circadian rhythms in Drosophila. , 2000, Cell.

[16]  C. Helfrich-Förster,et al.  Ectopic Expression of the Neuropeptide Pigment-Dispersing Factor Alters Behavioral Rhythms in Drosophila melanogaster , 2000, The Journal of Neuroscience.

[17]  Kevin P. Keegan,et al.  Drosophila Clock Can Generate Ectopic Circadian Clocks , 2003, Cell.

[18]  F. Jackson,et al.  A role for CK2 in the Drosophila circadian oscillator , 2003, Nature Neuroscience.

[19]  The FlyBase database of the Drosophila genome projects and community literature. , 2003, Nucleic acids research.

[20]  A. J. Schroeder,et al.  The FlyBase database of the Drosophila Genome Projects and community literature. , 2002, Nucleic acids research.

[21]  S. Hoare,et al.  Mechanisms of peptide and nonpeptide ligand binding to Class B G-protein-coupled receptors. , 2005, Drug discovery today.

[22]  P. Taghert,et al.  Neuropeptides and neuropeptide receptors in the Drosophila melanogaster genome. , 2001, Genome research.

[23]  S. Kay,et al.  A P Element with a Novel Fusion of Reporters Identifies regular, a C2H2 Zinc-Finger Gene Downstream of the Circadian Clock , 2002, Molecular and Cellular Neuroscience.

[24]  J. C. Hall,et al.  Differential regulation of circadian pacemaker output by separate clock genes in Drosophila. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Handler,et al.  Transplantation of a circadian pacemaker in Drosophila , 1979, Nature.

[26]  J. Truman,et al.  Sequential Nuclear Accumulation of the Clock Proteins Period and Timeless in the Pacemaker Neurons of Drosophila melanogaster , 2002, The Journal of Neuroscience.

[27]  José Agosto,et al.  Coupled oscillators control morning and evening locomotor behaviour of Drosophila , 2004, Nature.

[28]  R. Carthew,et al.  Making a better RNAi vector for Drosophila: use of intron spacers. , 2003, Methods.

[29]  J. C. Hall,et al.  The disconnected Visual System Mutations in Drosophila melanogaster Drastically Disrupt Circadian Rhythms , 1989, Journal of biological rhythms.

[30]  F. Netter,et al.  Supplemental References , 2002, We Came Naked and Barefoot.

[31]  François Rouyer,et al.  Morning and evening peaks of activity rely on different clock neurons of the Drosophila brain , 2004, Nature.

[32]  Uwe Homberg,et al.  Pigment‐dispersing hormone‐immunoreactive neurons in the nervous system of wild‐type Drosophila melanogaster and of several mutants with altered circadian rhythmicity , 1993, The Journal of comparative neurology.

[33]  M. W. Young,et al.  Posttranscriptional and Posttranslational Regulation of Clock Genes , 2004, Journal of biological rhythms.

[34]  M. Kaneko.  Neural substrates of Drosophila rhythms revealed by mutants and molecular manipulations , 1998, Current Opinion in Neurobiology.

[35]  D. Finnegan,et al.  Nucleotide sequence of terminal repeats of 412 transposable elements of Drosophila melanogaster. A similarity to proviral long terminal repeats and its implications for the mechanism of transposition. , 1981, Journal of molecular biology.

[36]  A. Sehgal,et al.  Role of Molecular Oscillations in Generating Behavioral Rhythms in Drosophila , 2001, Neuron.

[37]  C. Helfrich-Förster.  Robust circadian rhythmicity of Drosophila melanogaster requires the presence of lateral neurons: a brain-behavioral study of disconnected mutants , 1998, Journal of Comparative Physiology A.

[38]  P. Hardin.  Transcription Regulation within the Circadian Clock: The E-box and Beyond , 2004, Journal of biological rhythms.

[39]  W. Fischer,et al.  A Soluble Form of the First Extracellular Domain of Mouse Type 2β Corticotropin-releasing Factor Receptor Reveals Differential Ligand Specificity* , 2003, The Journal of Biological Chemistry.