Significance of DopEcR, a G-protein coupled dopamine/ecdysteroid receptor, in physiological and behavioral response to stressors.

Organisms respond to various environmental stressors by modulating physiology and behavior to maintain homeostasis. Steroids and catecholamines are involved in the highly conserved signaling pathways crucial for mounting molecular and cellular events that ensure immediate or long-term survival under stress conditions. The insect dopamine/ecdysteroid receptor (DopEcR) is a dual G-protein coupled receptor for the catecholamine dopamine and the steroid hormone ecdysone. DopEcR acts in a ligand-dependent manner, mediating dopaminergic signaling and unconventional "nongenomic" ecdysteroid actions through various intracellular signaling pathways. This unique feature of DopEcR raises the interesting possibility that DopEcR may serve as an integrative hub for complex molecular cascades activated under stress conditions. Here, we review previously published studies of Drosophila DopEcR in the context of stress response and also present newly discovered DopEcR loss-of-function phenotypes under different stress conditions. These findings provide corroborating evidence that DopEcR plays vital roles in responses to various stressors, including heat, starvation, alcohol, courtship rejection, and repeated neuronal stimulation in Drosophila. We further discuss what is known about DopEcR in other insects and DopEcR orthologs in mammals, implicating their roles in stress responses. Overall, this review highlights the importance of dual GPCRs for catecholamines and steroids in modulating physiology and behavior under stress conditions. Further multidisciplinary studies of Drosophila DopEcR will contribute to our basic understanding of the functional roles and underlying mechanisms of this class of GPCRs.