Conformational specificity of opioid receptors is determined by subcellular location irrespective of agonist

Autor: Manojkumar A. Puthenveedu, Wooree Ko, Stephanie E Crilly, Zara Y. Weinberg
Rok vydání: 2021
Předmět:
0301 basic medicine
organelle
Protein Conformation
Golgi Apparatus
Biosensing Techniques
Ligands
PC12 Cells
Piperazines
GPCR
0302 clinical medicine
Receptors
Opioid
delta
Cyclic AMP
Biology (General)
Receptor
beta-Arrestins
Neurons
Chemistry
Effector
General Neuroscience
General Medicine
Ligand (biochemistry)
Cell biology
Benzamides
symbols
Medicine
signaling
Research Article
medicine.drug
Agonist
QH301-705.5
medicine.drug_class
Science
General Biochemistry
Genetics and Molecular Biology
Structure-Activity Relationship
03 medical and health sciences
symbols.namesake
Live cell imaging
Organelle
Arrestin
medicine
Animals
G protein-coupled receptor
General Immunology and Microbiology
Cell Membrane
spatial encoding
Cell Biology
Golgi apparatus
Rats
030104 developmental biology
Microscopy
Fluorescence
Opioid
Rat
030217 neurology & neurosurgery
Zdroj: eLife
eLife, Vol 10 (2021)
ISSN: 2050-084X
Popis: The prevailing model for the variety in drug responses is that they stabilize distinct active states of their G protein-coupled receptor (GPCR) targets, allowing coupling to different effectors. However, whether the same ligand can produce different GPCR active states based on the environment of receptors in cells is a fundamental unanswered question. Here we address this question using live cell imaging of conformational biosensors that read out distinct active conformations of the δ-opioid receptor (DOR), a physiologically relevant GPCR localized to Golgi and the surface in neurons. We show that, although Golgi and surface pools of DOR regulated cAMP, the two pools engaged distinct conformational biosensors in response to the same ligand. Further, DOR recruited arrestin on the plasma membrane but not the Golgi. Our results suggest that the same agonist drives different conformations of a GPCR at different locations, allowing receptor coupling to distinct effectors at different locations.
Databáze: OpenAIRE
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