| First Author | Mittal N | Year | 2013 |
| Journal | Cell Rep | Volume | 5 |
| Issue | 4 | Pages | 1010-21 |
| PubMed ID | 24239352 | Mgi Jnum | J:205521 |
| Mgi Id | MGI:5545699 | Doi | 10.1016/j.celrep.2013.10.015 |
| Citation | Mittal N, et al. (2013) Select G-protein-coupled receptors modulate agonist-induced signaling via a ROCK, LIMK, and beta-arrestin 1 pathway. Cell Rep 5(4):1010-21 |
| abstractText | 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 (deltaORs) activate cofilin through Rho-associated coiled-coil-containing protein kinase (ROCK), LIM domain kinase (LIMK), and beta-arrestin 1 (beta-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 beta-arr1. Functional evidence of this cascade was demonstrated in vivo, where the behavioral effects of deltaOR or ORL1 agonists were enhanced in the absence of beta-arr1 or prevented by inhibiting ROCK. This pathway allows deltaOR and ORL1 agonists to rapidly regulate receptor function. |
