title: 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.
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 P2Y(1), P2Y(2), P2Y(4), and P2Y(11), 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 P2Y(4) 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.
authors.affiliation: Institut für Neurobiochemie, Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Magdeburg, Germany.
authors.forename: Weibo
authors.initials: W
authors.lastname: Luo
authors.forename: Yingfei
authors.initials: Y
authors.lastname: Wang
authors.forename: Georg
authors.initials: G
authors.lastname: Reiser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D044464:Receptor, PAR-2 / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D044462:Receptors, Proteinase-Activated / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058470:Receptors, Purinergic P2Y / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000502:physiology*; D033921:Vesicular Transport Proteins
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D044464:Receptor, PAR-2; D017450:Receptors, Opioid, mu; D044462:Receptors, Proteinase-Activated; D018048:Receptors, Purinergic P2; D058470:Receptors, Purinergic P2Y; C524397:TMED2 protein, human; D033921:Vesicular Transport Proteins; C104749:purinoceptor P2Y4; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups)