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J Biol Chem. 2010 Sep 24;285(39):30115-25. doi: 10.1074/jbc.M110.141549. Epub 2010 Jul 22.

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

Author information

1
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

β-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 β-arrestins for atypical 7TMRs and non-7TM receptors have emerged. Here, we uncover an entirely novel regulatory role of β-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 β-arrestin 1 to this complex. Surprisingly, angiotensin stimulation results in ubiquitination of TRPV4, a process that requires β-arrestin 1, and subsequently to internalization and functional down-regulation of TRPV4. β-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 β-arrestins and TRPV4 and uncovers an entirely novel mechanism to maintain appropriate intracellular Ca(2+) concentration to avoid excessive Ca(2+) signaling.

PMID:
20650893
PMCID:
PMC2943294
DOI:
10.1074/jbc.M110.141549
[Indexed for MEDLINE]
Free PMC Article

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