Search

Canonically, G-protein-coupled receptor (GPCR) signaling is transient and confined to the plasma membrane (PM). Deviating from this paradigm, the parathyroid hormone receptor (PTHR1) stimulates sustained G s signaling at endosomes. In addition to G s , PTHR1 activates G q signaling; yet, in contrast to the PTHR1-G s pathway, the spatiotemporal dynamics of the G q branch of PTHR1 signaling and its relationship to G s signaling remain largely ill defined. Recognizing that a downstream consequence of G q signaling is the activation of phospholipase D (PLD) enzymes, we leverage activity-based, bioorthogonal imaging tools for PLD signaling to visualize and quantify the G q branch of PTHR1 signaling. We establish that PTHR1-G q signaling is short lived, exclusively at the PM, and antagonized by PTHR1 endocytosis. Our data support a model wherein G q and G s compete for ligand-bound receptors at the PM and more broadly highlight the utility of bioorthogonal tools for imaging PLDs as probes to visualize GPCR-G q signaling., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)