Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV1

Title: β-Arrestin-2 desensitizes the transient receptor potential vanilloid 1 (TRPV1) channel.

Authors: Elaine D Por, Sonya M Bierbower, Kelly A Berg, Ruben Gomez, Armen N Akopian, William C Wetsel, Nathaniel A Jeske

Journal, date & volume: J. Biol. Chem., 2012 Oct 26 , 287, 37552-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22952227

Abstract
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 β-arrestin-2 as a scaffolding protein that regulates TRPV1 receptor activity. We report β-arrestin-2 association with TRPV1 in multiple cell models. Moreover, siRNA-mediated knockdown of β-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 β-arrestin-2 knock-out mice compared with wild type. In addition, we found that β-arrestin-2 scaffolding of phosphodiesterase PDE4D5 to the plasma membrane was required for TRPV1 desensitization. Importantly, inhibition of PDE4D5 activity reversed β-arrestin-2 desensitization of TRPV1. Together, these results identify a new endogenous scaffolding mechanism that regulates TRPV1 ligand binding and activation.