Identification of a novel recycling sequence in the C-tail of FPR2/ALX receptor: association with cell protection from apoptosis.

Abstract

Formyl-peptide receptor type 2 (FPR2; also called ALX because it is the receptor for lipoxin A4) sustains a variety of biological responses relevant to the development and control of inflammation, yet the cellular regulation of this G-protein-coupled receptor remains unexplored. Here we report that, in response to peptide agonist activation, FPR2/ALX undergoes β-arrestin-mediated endocytosis followed by rapid recycling to the plasma membrane. We identify a transplantable recycling sequence that is both necessary and sufficient for efficient receptor recycling. Furthermore, removal of this C-terminal recycling sequence alters the endocytic fate of FPR2/ALX and evokes pro-apoptotic effects in response to agonist activation. This study demonstrates the importance of endocytic recycling in the anti-apoptotic properties of FPR2/ALX and identifies the molecular determinant required for modulation of this process fundamental for the control of inflammation.

• Authors: Dawn Thompson, Simon McArthur, James N Hislop, Roderick J Flower, Mauro Perretti
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 289 Issue 52 Pg. 36166-78 (Dec 26 2014) ISSN: 1083-351X [Electronic] United States
• PMID: 25326384 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Arrestins
• FPR2 protein, human
• Receptors, Formyl Peptide
• Receptors, Lipoxin
• beta-Arrestins

Topics

• Amino Acid Sequence
• Apoptosis
• Arrestins (metabolism)
• HEK293 Cells
• Humans
• MAP Kinase Signaling System
• Molecular Sequence Data
• Protein Binding
• Protein Structure, Tertiary
• Protein Transport
• Receptors, Formyl Peptide (chemistry, metabolism)
• Receptors, Lipoxin (chemistry, metabolism)
• beta-Arrestins