| First Author | Por ED | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 44 | Pages | 37552-63 |
| PubMed ID | 22952227 | Mgi Jnum | J:192132 |
| Mgi Id | MGI:5464072 | Doi | 10.1074/jbc.M112.391847 |
| Citation | Por ED, et al. (2012) beta-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1) channel. J Biol Chem 287(44):37552-63 |
| abstractText | Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel activated by multiple stimuli and is implicated in a variety of pain disorders. Dynamic sensitization of TRPV1 activity by A-kinase anchoring protein 150 demonstrates a critical role for scaffolding proteins in nociception, yet few studies have investigated scaffolding proteins capable of mediating receptor desensitization. In this study, we identify beta-arrestin-2 as a scaffolding protein that regulates TRPV1 receptor activity. We report beta-arrestin-2 association with TRPV1 in multiple cell models. Moreover, siRNA-mediated knockdown of beta-arrestin-2 in primary cultures resulted in a significant increase in both initial and repeated responses to capsaicin. Electrophysiological analysis further revealed significant deficits in TRPV1 desensitization in primary cultures from beta-arrestin-2 knock-out mice compared with wild type. In addition, we found that beta-arrestin-2 scaffolding of phosphodiesterase PDE4D5 to the plasma membrane was required for TRPV1 desensitization. Importantly, inhibition of PDE4D5 activity reversed beta-arrestin-2 desensitization of TRPV1. Together, these results identify a new endogenous scaffolding mechanism that regulates TRPV1 ligand binding and activation. |
