Rapid, nongenomic responses to ecdysteroids and catecholamines mediated by a novel Drosophila G-protein-coupled receptor.
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 beta-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 "gamma-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.
The Inositide Laboratory, The Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Deepak P
DP
Srivastava
Esther J
EJ
Yu
Karen
K
Kennedy
Heather
H
Chatwin
Vincenzina
V
Reale
Maureen
M
Hamon
Trevor
T
Smith
Peter D
PD
Evans
D000818:Animals; D016466:CHO Cells; D002395:Catecholamines / Q000502:physiology*; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D009865:Oocytes / Q000502:physiology; D016133:Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015183:Restriction Mapping; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014982:Xenopus laevis
D002395:Catecholamines; D017931:DNA Primers; D018076:DNA, Complementary; D029721:Drosophila Proteins; D043562:Receptors, G-Protein-Coupled