N-formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation

49Citations
Citations of this article
49Readers
Mendeley users who have this article in their library.

Abstract

Among human N-formyl peptide chemoattractant receptors, FPR2/ALX and FPR3 share the highest degree of amino acid identity (83%), and trigger similar cell responses upon ligand binding. Although FPR2/ALX is a promiscuous receptor, FPR3 has only one specific high affinity ligand, F2L, and a more restricted tissue/cell distribution. In this study, we showed that FPR2/ALX behaved as the prototypical receptor FPR1. The agonist-dependent phosphorylation used a hierarchical mechanism with a prominent role of Ser 329, Thr 332, and Thr 335. Phosphorylation of FPR2/ALX was essential for its desensitization but the lack of phosphorylation did not result in enhanced or sustained responses. In contrast, resting FPR3 displayed a marked level of phosphorylation, which was only slightly increased upon agonist stimulation. Another noticeable difference between the two receptors was their subcellular distribution in unstimulated cells. Although FPR2/ALX was evenly distributed at the plasma membrane FPR3 was localized in small intracellular vesicles. By swapping domains between FPR2/ALX and FPR3, we uncovered the determinants involved in the basal phosphorylation of FPR3. Experiments aimed at monitoring receptor-bound antibody uptake showed that the intracellular distribution of FPR3 resulted from a constitutive internalization that was independent of C terminus phosphorylation. Unexpectedly, exchanging residues 1 to 53, which encompass the N-terminal extracellular region and the first transmembrane domain, between FPR2/ALX and FPR3 switched localization of the receptors from the plasma membrane to intracellular vesicles and vice versa. A clathrin-independent, possibly caveolae-dependent, mechanism was involved in FPR3 constitutive internalization. The peculiar behavior of FPR3 most probably serves distinct physiological functions that remain largely unknown. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

References Powered by Scopus

β-Arrestin acts as a clathrin adaptor in endocytosis of the β<inf>2</inf>- adrenergic receptor

1230Citations
N/AReaders
Get full text

Induction of mutant dynamin specifically blocks endocytic coated vesicle formation

1071Citations
N/AReaders
Get full text

International union of basic and clinical pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family

656Citations
N/AReaders
Get full text

Cited by Powered by Scopus

International union of basic and clinical pharmacology. LXXXVII. complement peptide C5a, C4a, and C3a receptors

215Citations
N/AReaders
Get full text

The role of formylated peptides and formyl peptide receptor 1 in governing neutrophil function during acute inflammation

202Citations
N/AReaders
Get full text

An overview of the diverse roles of G-protein coupled receptors (GPCRs) in the pathophysiology of various human diseases

164Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

APA

Rabiet, M. J., Macari, L., Dahlgren, C., & Boulay, F. (2011). N-formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation. Journal of Biological Chemistry, 286(30), 26718–26731. https://doi.org/10.1074/jbc.M111.244590

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 19

63%

Researcher 9

30%

Professor / Associate Prof. 1

3%

Lecturer / Post doc 1

3%

Readers' Discipline

Tooltip

Biochemistry, Genetics and Molecular Bi... 10

32%

Pharmacology, Toxicology and Pharmaceut... 9

29%

Agricultural and Biological Sciences 8

26%

Medicine and Dentistry 4

13%

Article Metrics

Tooltip
Mentions
References: 1

Save time finding and organizing research with Mendeley

Sign up for free