Visualizing GPCR 'Megaplexes' Which Enable Sustained Intracellular Signaling.
A range of cutting-edge techniques have been employed to visualize 'megaplexes' consisting of a G protein-coupled receptor (GPCR) bound to β-arrestin in intracellular endosomes following agonist-induced internalization. Surprisingly, the complex includes simultaneous binding of the heterotrimeric G protein, which retains full functional activity and supports sustained signaling from within the cell.
Heptares Therapeutics Ltd, Biopark, Welwyn Garden City, Hertfordshire, AL7 3AX, UK. Electronic address: fiona.marshall@heptares.com.
Fiona H
FH
Marshall
D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D060807:Bioluminescence Resonance Energy Transfer Techniques; D015374:Biosensing Techniques / Q000379:methods; D000242:Cyclic AMP / Q000096:biosynthesis*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008958:Models, Molecular; D015335:Molecular Probes / Q000737:chemistry; D011412:Propanolamines / Q000494:pharmacology; D011485:Protein Binding; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071559:beta-Arrestin 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C000605253:ARRB1 protein, human; D058666:Adrenergic beta-2 Receptor Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D015335:Molecular Probes; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D017483:Receptors, Vasopressin; D011993:Recombinant Fusion Proteins; D000071559:beta-Arrestin 1; C026777:ICI 118551; D000242:Cyclic AMP; D003894:Deamino Arginine Vasopressin; D007545:Isoproterenol