<i>Drosophila melanogaster</i>G Protein–Coupled Receptors

Brody, Theodore M.; Cravchik, Anibal

doi:10.1083/jcb.150.2.f83

Cited by 252 publications

(224 citation statements)

References 41 publications

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“…Likewise, these receptors did not display any changes in intracellular calcium levels in response to Ast-C application, with or without a co-expressed promiscuous G␣ protein subunit. 2 The C termini of these receptors have multiple clusters of serine/threonine residues that are potential targets for GRK phosphorylation (23). We reasoned that this lack of a detectable response to Ast-C might be due to intrinsic phosphorylation by the endogenous complement of GRKs.…”

Section: Resultsmentioning

confidence: 99%

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Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

Johnson

Bohn

Barak

et al. 2003

Journal of Biological Chemistry

119

108

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Activation of G protein-coupled receptors (GPCR)leads to the recruitment of ␤-arrestins. By tagging the ␤-arrestin molecule with a green fluorescent protein, we can visualize the activation of GPCRs in living cells. We have used this approach to de-orphan and study 11 GPCRs for neuropeptide receptors in Drosophila melanogaster. Here we verify the identities of ligands for several recently de-orphaned receptors, including the receptors for the Drosophila neuropeptides proctolin (CG6986), neuropeptide F (CG1147), corazonin (CG10698), dFMRF-amide (CG2114), and allatostatin C (CG7285 and CG13702). We also de-orphan CG6515 and CG7887 by showing these two suspected tachykinin receptor family members respond specifically to a Drosophila tachykinin neuropeptide. Additionally, the translocation assay was used to de-orphan three Drosophila receptors. We show that CG14484, encoding a receptor related to vertebrate bombesin receptors, responds specifically to allatostatin B. Furthermore, the pair of paralogous receptors CG8985 and CG13803 responds specifically to the FMRF-amide-related peptide dromyosuppressin. To corroborate the findings on orphan receptors obtained by the translocation assay, we show that dromyosuppressin also stimulated GTP␥S binding and inhibited cAMP by CG8985 and CG13803. Together these observations demonstrate the ␤-arrestin-green fluorescent protein translocation assay is an important tool in the repertoire of strategies for ligand identification of novel G protein-coupled receptors.

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Section: Resultsmentioning

confidence: 99%

“…The recent sequencing of the Drosophila melanogaster genome (1) has enabled the identification of the entire complement of ϳ160 fly GPCRs 1 (2). Of these, 44 encode GPCRs for peptide ligands (3) of which approximately half have been functionally characterized.…”

mentioning

confidence: 99%

Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

Johnson

Bohn

Barak

et al. 2003

Journal of Biological Chemistry

119

108

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“…Alternatively, the role of CCAP may change during postembryonic development because of changes in the expression of CCAP receptors. Although the CCAP receptor has not been conclusively identified (but see Park et al, 2002b), the completion of the Drosophila genome sequence and its subsequent analyses has produced a list of potential candidates (Brody and Cravchik, 2000;Hewes and Taghert, 2001). …”

Section: Bases For the Changing Roles For Ccap During Postembryonic Dmentioning

confidence: 99%

Targeted ablation of CCAP neuropeptide-containing neurons ofDrosophilacauses specific defects in execution and circadian timing of ecdysis behavior

et al. 2003

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Insect growth and metamorphosis is punctuated by molts, during which a new cuticle is produced. Every molt culminates in ecdysis, the shedding of the remains of the old cuticle. Both the timing of ecdysis relative to the molt and the actual execution of this vital insect behavior are under peptidergic neuronal control. Based on studies in the moth, Manduca sexta, it has been postulated that the neuropeptide Crustacean cardioactive peptide (CCAP)plays a key role in the initiation of the ecdysis motor program. We have used Drosophila bearing targeted ablations of CCAP neurons (CCAP KO animals) to investigate the role of CCAP in the execution and circadian regulation of ecdysis. CCAP KO animals showed specific defects at ecdysis, yet the severity and nature of the defects varied at different developmental stages. The majority of CCAP KO animals died at the pupal stage from the failure of pupal ecdysis, whereas larval ecdysis and adult eclosion behaviors showed only subtle defects. Interestingly, the most severe failure seen at eclosion appeared to be in a function required for abdominal inflation, which could be cardioactive in nature. Although CCAP KO populations exhibited circadian eclosion rhythms, the daily distribution of eclosion events (i.e.,gating) was abnormal. Effects on the execution of ecdysis and its circadian regulation indicate that CCAP is a key regulator of the behavior. Nevertheless, an unexpected finding of this work is that the primary functions of CCAP as well as its importance in the control of ecdysis behaviors may change during the postembryonic development of Drosophila.

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“…Analysis of the completed Drosophila genomic sequences (22,23) identified Ͼ100 genes encoding G protein-coupled receptors (GPCRs). Further analysis indicated that 44 such receptors are likely to have peptide ligands and that the majority of these are derived from ancestors for mammalian peptide GPCR genes (24).…”

mentioning

confidence: 99%

Identification and characterization of a G protein-coupled receptor for the neuropeptide proctolin in Drosophila melanogaster

Johnson

Garczynski

Park

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Proctolin is a bioactive neuropeptide that modulates interneuronal and neuromuscular synaptic transmission in a wide variety of arthropods. We present several lines of evidence to propose that the orphan G protein-coupled receptor CG6986 of Drosophila is a proctolin receptor. When expressed in mammalian cells, CG6986 confers second messenger activation after proctolin application, with an EC 50 of 0.3 nM. In competition-based studies, the CG6986 receptor binds proctolin with high affinity (IC50 ‫؍‬ 4 nM). By microarray analysis, CG6986 transcript is consistently detected in head mRNA of different genotypes, and under different environmental conditions. By blot analysis, anti-CG6986 antibodies detect a band in tissue homogenates similar to the predicted size of the protein. Proctolin receptor immunosignals are found in the hindgut, heart, and in distinct neuronal populations of the CNS; such patterns correlate with previous demonstrations of proctolin biological activity, and in several instances, with areas of proctolin peptide immunosignals. The identification of a bona fide proctolin receptor provides the basis for a mechanistic analysis of this critical synaptic modulator.T he pentapeptide proctolin (RYLPT) was the first neuropeptide to be isolated and sequenced from insects (1). It was purified based on its myotropic actions on the insect hindgut, and was subsequently found to have wide distribution throughout the arthropods (2-4). In the crab Cancer, proctolin has potent effects on defined neural circuits within the stomatogastric system (5) and at the neuromuscular junction (6). In insects, proctolin is a major peptide cotransmitter and it modulates contractions of both somatic and visceral muscles (7,8). Proctolin-like immunosignals are found within a small number of neurons in the larval CNS of Drosophila and these include efferents to bodywall muscles, heart, and viscera (9).The mechanisms of actions of proctolin have also been investigated. Proctolin elevates levels of inositol trisphosphate (IP 3 ) and cAMP, and increases calcium entry through voltagegated ion channels (10-13). Several studies have suggested the existence of multiple proctolin receptor subtypes based on binding studies and activities of proctolin (14, 15) or its structural analogues (16-19). However, more recent studies (15,20,21) of proctolin binding support a model featuring a single proctolin receptor. The identification of a specific proctolin receptor will help address issues regarding possibilities of multiple receptors, the precise nature of proctolin-dependent signaling pathways, and phylogenetic differences in proctolin signaling. The significance of such studies is substantial because proctolin exerts such a widespread role as a synaptic modulator in arthropod physiology.Analysis of the completed Drosophila genomic sequences (22, 23) identified Ͼ100 genes encoding G protein-coupled receptors (GPCRs). Further analysis indicated that 44 such receptors are likely to have peptide ligands and that the majority of these are derive...

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Drosophila melanogasterG Protein–Coupled Receptors

Cited by 252 publications

References 41 publications

Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

Identification of Drosophila Neuropeptide Receptors by G Protein-coupled Receptors-β-Arrestin2 Interactions

Targeted ablation of CCAP neuropeptide-containing neurons ofDrosophilacauses specific defects in execution and circadian timing of ecdysis behavior

Identification and characterization of a G protein-coupled receptor for the neuropeptide proctolin in Drosophila melanogaster

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