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

doi:10.1016/j.celrep.2013.10.015

Cell Reports (Nov 2013)

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

Affiliations

Nitish Mittal: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Kristofer Roberts: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Katsuri Pal: Division of Biomedical Sciences, Cell, Molecular, and Developmental Biology Program, University of California, Riverside, Riverside, CA 92521, USA
Laurent A. Bentolila: Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA
Elissa Fultz: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Ani Minasyan: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Catherine Cahill: Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, CA 92697, USA
Amynah Pradhan: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
David Conner: Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Kathryn DeFea: Division of Biomedical Sciences, Cell, Molecular, and Developmental Biology Program, University of California, Riverside, Riverside, CA 92521, USA
Christopher Evans: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA
Wendy Walwyn: Department of Psychiatry and Biobehavioral Sciences, Stefan Hatos Center for Neuropharmacology, Semel Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA

DOI: https://doi.org/10.1016/j.celrep.2013.10.015
Journal volume & issue: Vol. 5, no. 4
pp. 1010 – 1021

Abstract

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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 in vivo, 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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