Differential regulation of two palmitoylation sites in the cytoplasmic tail of the β1-adrenergic receptor

David M. Zuckerman, Stuart W. Hicks, Guillaume Charron, Howard C. Hang, Carolyn E. Machamer

Research output: Contribution to journalArticlepeer-review

Abstract

S-Palmitoylation of G protein-coupled receptors (GPCRs) is a prevalent modification, contributing to the regulation of receptor function. Despite its importance, the palmitoylation status of the β1-adrenergic receptor, a GPCR critical for heart function, has never been determined. We report here that the β1-adrenergic receptor is palmitoylated on three cysteine residues at two sites in the C-terminal tail. One site (proximal) is adjacent to the seventh transmembrane domain and is a consensus site for GPCRs, and the other (distal) is downstream. These sites are modified in different cellular compartments, and the distal palmitoylation site contributes to efficient internalization of the receptor following agonist stimulation. Using a bioorthogonal palmitate reporter to quantify palmitoylation accurately, we found that the rates of palmitate turnover at each site are dramatically different. Although palmitoylation at the proximal site is remarkably stable, palmitoylation at the distal site is rapidly turned over. This is the first report documenting differential dynamics of palmitoylation sites in a GPCR. Our results have important implications for function and regulation of the clinically important β1-adrenergic receptor.

Original languageEnglish (US)
Pages (from-to)19014-19023
Number of pages10
JournalJournal of Biological Chemistry
Volume286
Issue number21
DOIs
StatePublished - May 27 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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