Constitutively active GPR6 is located in the intracellular compartments
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Updated: Jun 27, 2026

Detection of Ligand-activated G Protein-coupled Receptor Internalization by Confocal Microscopy
Published on: April 9, 2017
Shalini Padmanabhan1, Amanda G Myers, Balakrishna M Prasad
1Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912, USA.
Abstract:
We used multiple imaging assays to test the hypothesis that GPR6, a constitutively active Gs-coupled receptor, is present on the cell surface. A pHluorin tag at the N-terminus of rat GPR6 expressed in human embryonic kidney 293 (HEK293) cells was not accessible to protons, chymotrypsin or anti-green fluorescent protein antibody, demonstrating that GPR6 is primarily located in intracellular compartments. Similar intracellular localization of pHluorin-tagged GPR6 was found in striatal neurons, where endogenous GPR6 is expressed. Confirmation of Gs-mediated constitutive activity in HEK293 cells and striatal neurons led us to conclude that GPR6 can signal from intracellular compartments.
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