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Arresting a transient receptor potential (TRP) channel: beta-arrestin 1 mediates ubiquitination and functional down-regulation of TRPV4.

Authors: Shukla, AK  Kim, J  Ahn, S  Xiao, K  Shenoy, SK  Liedtke, W  Lefkowitz, RJ 
Citation: Shukla AK, etal., J Biol Chem. 2010 Sep 24;285(39):30115-25. Epub 2010 Jul 22.
Pubmed: (View Article at PubMed) PMID:20650893
DOI: Full-text: DOI:10.1074/jbc.M110.141549

beta-Arrestins, originally discovered to desensitize activated G protein-coupled receptors, (aka seven-transmembrane receptors, 7TMRs) also mediate 7TMR internalization and G protein-independent signaling via these receptors. More recently, several regulatory roles of beta-arrestins for atypical 7TMRs and non-7TM receptors have emerged. Here, we uncover an entirely novel regulatory role of beta-arrestins in cross-talk between the angiotensin receptor (AT1aR) and a member of the transient receptor potential (TRP) ion channel family, TRPV4. AT1aR and TRPV4 form a constitutive complex in the plasma membrane, and angiotensin stimulation leads to recruitment of beta-arrestin 1 to this complex. Surprisingly, angiotensin stimulation results in ubiquitination of TRPV4, a process that requires beta-arrestin 1, and subsequently to internalization and functional down-regulation of TRPV4. beta-Arrestin 1 interacts with, and acts as an adaptor for AIP4, an E3 ubiquitin ligase responsible for TRPV4 ubiquitination. Thus, our data provide the first evidence of a functional link between beta-arrestins and TRPV4 and uncovers an entirely novel mechanism to maintain appropriate intracellular Ca(2+) concentration to avoid excessive Ca(2+) signaling.


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CRRD Object Information
CRRD ID: 5509917
Created: 2011-11-11
Species: All species
Last Modified: 2011-11-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.