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.
Srivastava
Deepak P
DP
The Inositide Laboratory, The Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Yu
Esther J
EJ
Kennedy
Karen
K
Chatwin
Heather
H
Reale
Vincenzina
V
Hamon
Maureen
M
Smith
Trevor
T
Evans
Peter D
PD
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