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

Abstract

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.

Keywords:

• Stress
• GPCR
• nongenomic steroid action
• catecholamine
• Drosophila

Acknowledgements

We thank the late Dr. Troy Zars (University of Missouri Columbia) for his long-term consistent friendship and fruitful discussions about the DopEcR project and other scientific issues. We dedicate this paper to Dr. Zars. We also thank members of the Kitamoto lab for technical assistance and the Bloomington Stock Center and VDRC for fly stocks.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the following grants and fellowships: NIH R03AA021968 (TK), NIH R01MH085081 (TK), NSF IOS1352882 (TK), NIH F31AA021625 (EP), NIH T32NS045549 (EP, AL), NIH T32NS007421 (AL), Chateaubriand Fellowship (AL), University of Iowa Graduate College Dean’s Graduate Fellowship (AL), NIH T32GM008629 (JM), and NIH T32NS045549 (JM).