Abstract
G protein-coupled receptors (GPCRs) are regulated by kinases and phosphatases that control their phosphorylation state. Here, the possibility that the state of GPCR phosphorylation could be affected by paracrine input was explored. We show that dopamine increased the rate of dephosphorylation of rhodopsin, the light receptor, in intact frog retinas. Further, we found that rod outer segments from dopamine-treated retinas contained increased rhodopsin phosphatase activity, indicating that this effect of dopamine on rhodopsin was mediated by stimulation of rhodopsin phosphatase. Dopamine is a ubiquitous neuromodulator and, in the retina, is released from the inner cell layers. Thus, our results identify a pathway for feedback regulation of rhodopsin from the inner retina and illustrate the involvement of dopamine in paracrine regulation of the sensitivity of a GPCR.
Highlights
G protein-coupled receptors (GPCRs)1 represent a widespread family of proteins that transduce a large variety of signals, such as light, odorants, hormones, and neurotransmitters
Less is known about the dephosphorylation of GPCRs and the regulation of their phosphatases, rhodopsin dephosphorylation appears to be affected by Ca2ϩ levels
We demonstrate here that dopamine feedback to the photoreceptor cells affects the kinetics of rhodopsin dephosphorylation in intact frog retinas, indicating that the light receptor can be regulated by paracrine input
Summary
From the Departments of ‡Pharmacology and §Neurosciences, University of California at San Diego School of Medicine, La Jolla, California 92093-0983. G protein-coupled receptors (GPCRs) are regulated by kinases and phosphatases that control their phosphorylation state. G protein-coupled receptors (GPCRs) represent a widespread family of proteins that transduce a large variety of signals, such as light, odorants, hormones, and neurotransmitters They have common structural elements, including seven transmembrane domains, and are regulated by many homologous mechanisms. Regulation of kinases and phosphatases provides upstream mechanisms for modulating GPCRs. The focus of the present study was on whether input from the inner retina could affect the phosphorylation state of rhodopsin. We demonstrate here that dopamine feedback to the photoreceptor cells affects the kinetics of rhodopsin dephosphorylation in intact frog retinas, indicating that the light receptor can be regulated by paracrine input
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