Rapid, Nongenomic Responses to Ecdysteroids and Catecholamines Mediated by a Novel Drosophila G-Protein-Coupled Receptor
Open accessAbstract
Nongenomic response pathways mediate many of the rapid actions of steroid hormones, but the mechanisms underlying such responses remain controversial. In some cases, cell-surface expression of classical nuclear steroid receptors has been suggested to mediate these effects, but, in a few instances, specific G-protein-coupled receptors (GPCRs) have been reported to be responsible. Here, we describe the activation of a novel, neuronally expressed Drosophila GPCR by the insect ecdysteroids ecdysone (E) and 20-hydroxyecdysone (20E). This is the first report of an identified insect GPCR interacting with steroids. The Drosophila melanogaster dopamine/ecdysteroid receptor (DmDopEcR) shows sequence homology with vertebrate β-adrenergic receptors and is activated by dopamine (DA) to increase cAMP levels and to activate the phosphoinositide 3-kinase pathway. Conversely, E and 20E show high affinity for the receptor in binding studies and can inhibit the effects of DA, as well as coupling the receptor to a rapid activation of the mitogen-activated protein kinase pathway. The receptor may thus represent the Drosophila homolog of the vertebrate “γ-adrenergic receptors,” which are responsible for the modulation of various activities in brain, blood vessels, and pancreas. Thus, DmDopEcR can function as a cell-surface GPCR that may be responsible for some of the rapid, nongenomic actions of ecdysteroids, during both development and signaling in the mature adult nervous system.
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20E triggers intracellular rapid increases in Ca2+ and cAMP, and increases ERK phosphorylation in DmDopEcR overexpressing Sf9 cells.
“In addition, 20E triggers intracellular rapid increases in Ca2+ and cyclic adenosine monophosphate (cAMP), and increases ERK phosphorylation in the DmDopEcR overexpressing Sf9 cells [42].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [42]
DmDopEcR shows homology with vertebrate ARs.
“DmDopEcR shows homology with vertebrate ARs [24].”
From G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane (2014) · cites this paper as [24]
Several GPCRs bind with 20E, such as DmDopEcR binding with [3H]Pon A, or an unknown GPCR in the anterior silk gland of silkworms binding with [3H]Pon A.
“Numerous studies have reported the binding of several GPCRs with 20E, such as the binding of DmDopEcR with [3H]Pon A [24], or an unknown GPCR in the anterior silk gland of silkworms binding with [3H]Pon A [22].”
From G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane (2014) · cites this paper as [24]
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Ecdysteroid signalling in insects—From biosynthesis to gene expression regulation
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A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis
Regna, K., Kurshan, P. T., Harwood, B. N., Jenkins, A. M., Lai, C., Muskavitch, M. A. T., Kopin, A. S., & Draper, I. (2016) · BMC Developmental Biology · doi:10.1186/s12861-016-0115-z · Cited by 32 · see citing works
Jing, Y.-P., Wang, D., Han, X.-L., Dong, D.-J., Wang, J.-X., & Zhao, X.-F. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.706028 · Cited by 30 · see citing works
- Authors
- Srivastava, D. P., Yu, E. J., Kennedy, K., Chatwin, H., Reale, V., Hamon, M., Smith, T., & Evans, P. D.
- Affiliations
- Babraham Institute (GB)
- Northwestern University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-06-29
- Volume
- 25
- Issue
- 26
- Pages
- 6145-6155
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725065
- OpenAlex
- W2023092335
- Cited by
- 272
- References
- 114
- Citations by year
- 2026: 4 · 2025: 27 · 2024: 24 · 2023: 7 · 2022: 4 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 13 · 2017: 10 · 2016: 16 · 2015: 9 · 2014: 15 · 2013: 19 · 2012: 15
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- non-genomic steroid action, ecdysteroids, ecdysone, 20-hydroxyecdysone, G protein-coupled receptors, dopamine, catecholamines, cAMP signaling, phosphatidylinositol 3-kinase, mitogen-activated protein kinase, Drosophila melanogaster, neuronal receptors
- MeSH terms
- Animals, Catecholamines, Drosophila melanogaster, Female, Cricetinae, Oocytes, Transfection, Xenopus laevis, Restriction Mapping, Polymerase Chain Reaction, CHO Cells, DNA Primers, DNA, Complementary, Reverse Transcriptase Polymerase Chain Reaction, Drosophila Proteins, Receptors, G-Protein-Coupled
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