Select G-Protein-Coupled Receptors Modulate Agonist-Induced Signaling via a ROCK, LIMK, and β-Arrestin 1 Pathway

Nitish Mittal, Kristofer Roberts, Katsuri Pal, Laurent A. Bentolila, Elissa Fultz, Ani Minasyan, Catherine Cahill, Amynah Pradhan, David Conner, Kathryn DeFea, Christopher Evans, Wendy Walwyn

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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 (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 function,as assessed by agonist-induced inhibition of voltage-dependent Ca2+ channels in DRGs. Agonists of opioid-receptor-like receptors (ORL1) similarly influence the function of this receptor through ROCK, LIMK, and β-arr1. Functional evidence of this cascade was demonstrated invivo, where the behavioral effects of δOR or ORL1 agonists were enhanced in the absence of β-arr1 or prevented by inhibiting ROCK. This pathway allows δOR and ORL1 agonists to rapidly regulate receptor function

Original languageEnglish
Pages (from-to)1010-1021
Number of pages12
JournalCell Reports
Volume5
Issue number4
DOIs
StatePublished - Nov 27 2013

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