Proteinase-activated receptors, nucleotide P2Y receptors, and μ-opioid receptor-1B are under the control of the type I transmembrane proteins p23 and p24A in post-Golgi trafficking

Weibo Luo, Yingfie Wang, Georg Reiser

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

We recently characterized the proteinase-activated receptor (PAR)-2, a G protein-coupled receptor (GPCR), as the first cargo protein recognized by p24A. Here, we demonstrate that p24A binds to several other GPCRs, including PAR-1, the nucleotide receptors P2Y1, P2Y2, P2Y4, and P2Y11, as well as the μ-opioid receptor 1B. The acidic amino acid residues Glu and Asp at the second extracellular loop of GPCRs are essential for interaction with p24A. p23, another member of the p24 family, also interacts with GPCRs, similar to p24A. However, p23 shows a delayed dissociation from PAR-2 after activation of PAR-2, compared to the dissociation between PAR-2 and p24A. p24A and p23 arrest both P2Y4 receptor and μ-opioid receptor 1B at the intracellular compartments, as observed for PAR-2. A comparable result was obtained when we studied primary rat astrocytes in culture. Over-expression of the N-terminal p24A fragment impairs PAR-2 resensitization in astrocytes that extends our findings to a native system. In summary, we demonstrate that p24A and p23 are specific cargo receptors of GPCRs and differentially control GPCR trafficking in the biosynthetic pathway, and thereby, p24A and p23 regulate GPCR signaling in astrocytes.

Original languageEnglish (US)
Pages (from-to)71-81
Number of pages11
JournalJournal of Neurochemistry
Volume117
Issue number1
DOIs
StatePublished - Apr 1 2011

Keywords

  • Cargo
  • Cargo receptor
  • G protein-coupled receptor
  • Opioid receptor
  • P2y receptor
  • Proteinase-activated receptor
  • Receptor trafficking

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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