Abstract
The neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenomedullin
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Animals
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Animals, Genetically Modified
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Behavior, Animal / physiology
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Blotting, Western / methods
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Brain / cytology
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Brain / metabolism
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Calcitonin / pharmacology
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Cell Line
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Circadian Rhythm / physiology*
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Dose-Response Relationship, Drug
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Drosophila
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Drosophila Proteins / genetics
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Drosophila Proteins / pharmacology
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Drosophila Proteins / physiology*
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Gene Expression Regulation / physiology
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Genes, Insect
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Humans
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Immunohistochemistry / methods
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Maze Learning
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Motor Activity / genetics
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Motor Activity / physiology
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Mutagenesis / physiology
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Mutation
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Nerve Tissue Proteins / physiology
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Neurons / metabolism
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Neuropeptides / pharmacology
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Neuropeptides / physiology
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Orientation / physiology*
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Peptides / pharmacology
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RNA, Messenger / biosynthesis
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / physiology*
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Transfection / methods
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ras GTPase-Activating Proteins / physiology
Substances
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Drosophila Proteins
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NF1 protein, Drosophila
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Nerve Tissue Proteins
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Neuropeptides
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Peptides
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RNA, Messenger
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Receptors, G-Protein-Coupled
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pdf protein, Drosophila
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ras GTPase-Activating Proteins
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Adrenomedullin
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Calcitonin