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Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and ?-arrestin 1 pathway.


ABSTRACT: G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (?ORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and ?-arrestin 1 (?-arr1) to regulate actin polymerization. This controls receptor function, as assessed by agonist-induced inhibition of voltage-dependent Ca(2+) channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and ?-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of ?OR or ORL1 agonists were enhanced in the absence of ?-arr1 or prevented by inhibiting ROCK. This pathway allows ?OR and ORL1 agonists to rapidly regulate receptor function.

SUBMITTER: Mittal N 

PROVIDER: S-EPMC3870884 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and β-arrestin 1 pathway.

Mittal Nitish N   Roberts Kristofer K   Pal Katsuri K   Bentolila Laurent A LA   Fultz Elissa E   Minasyan Ani A   Cahill Catherine C   Pradhan Amynah A   Conner David D   DeFea Kathryn K   Evans Christopher C   Walwyn Wendy W  

Cell reports 20131114 4


G-protein-coupled receptors (GPCRs) are typically present in a basal, inactive state but, when bound to an agonist, activate downstream signaling cascades. In studying arrestin regulation of opioid receptors in dorsal root ganglia (DRG) neurons, we find that agonists of delta opioid receptors (δORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and β-arrestin 1 (β-arr1) to regulate actin polymerization. This controls receptor func  ...[more]

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