Phosphorylation regulates TRPV1 association with β-arrestin-2

Elaine D. Por, Ruben Gomez, Armen N Akopian, Nathaniel Jeske

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Post-translational modifications in TRPV1 (transient receptor potential vanilloid 1) play a critical role in channel activity. Phosphorylation of serine/threonine residues within the N-and C-termini of TRPV1 are implicated in receptor sensitization and activation. Conversely, TRPV1 desensitization occurs via a calcium-dependent mechanism and leads to receptor dephosphorylation. Importantly, we recently demonstrated that TRPV1 association with β-arrestin-2 is critical to receptor desensitization via its ability to scaffold the phosphodiesterase PDE4D5 to the receptor, regulating TRPV1 phosphorylation. In the present study, we demonstrate that phosphorylation of TRPV1 and β-arrestin-2 regulates this association at the membrane.Under serum-free media conditions, we observed a significant decrease in TRPV1 and β-arrestin-2 association in transfected CHO (Chinese-hamster ovary) cells. Pharmacological activation of the kinases PKA (protein kinase A) and PKC (protein kinase C) led to a robust increase in TRPV1 and β-arrestin-2 association, whereas inhibition of PKA and PKC decreased association. Previously, we identified potential PKAresidues (Ser116, Thr 370) in the N-terminus of TRPV1 modulated by β-arrestin-2. In the present study we reveal that the phosphorylation status of Thr370 dictates the β- arrestin-2 and TRPV1 association. Furthermore, we demonstrate that CK2 (casein kinase 2)-mediated phosphorylation of β- arrestin-2 at Thr382 is critical for its association with TRPV1. Taken together, the findings of the present study suggest that phosphorylation controls the association of TRPV1 with β-arrestin-2.

Original languageEnglish (US)
Pages (from-to)101-109
Number of pages9
JournalBiochemical Journal
Volume451
Issue number1
DOIs
StatePublished - Apr 1 2013

Fingerprint

Arrestin
Phosphorylation
Association reactions
Cyclic AMP-Dependent Protein Kinases
vanilloid receptor subtype 1
beta-Arrestin 1
Chemical activation
Casein Kinase II
Serum-Free Culture Media
Phosphoric Diester Hydrolases
Threonine
Post Translational Protein Processing
Cricetulus
Scaffolds
Serine
Protein Kinase C
Ovary

Keywords

  • β-arrestin-2
  • Desensitization
  • Inflammation
  • Pain
  • Phosphorylation
  • Transient receptor potential vanilloid 1 (TRPV1)

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Phosphorylation regulates TRPV1 association with β-arrestin-2. / Por, Elaine D.; Gomez, Ruben; Akopian, Armen N; Jeske, Nathaniel.

In: Biochemical Journal, Vol. 451, No. 1, 01.04.2013, p. 101-109.

Research output: Contribution to journalArticle

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