title: 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.affiliation: From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom and the School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom dthompson@abdn.ac.uk.
authors.forename: Dawn
authors.initials: D
authors.lastname: Thompson
authors.affiliation: From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom and.
authors.forename: Simon
authors.initials: S
authors.lastname: McArthur
authors.affiliation: the School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, Scotland, United Kingdom.
authors.forename: James N
authors.initials: JN
authors.lastname: Hislop
authors.affiliation: From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom and.
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Flower
authors.affiliation: From the William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom and m.perretti@qmul.ac.uk.
authors.forename: Mauro
authors.initials: M
authors.lastname: Perretti
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D019390:Arrestins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D044042:Receptors, Formyl Peptide / Q000737:chemistry / Q000378:metabolism*; D044067:Receptors, Lipoxin / Q000737:chemistry / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; C105101:FPR2 protein, human; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D000071557:beta-Arrestins
keywords: Apoptosis; Arrestin; Cell Sorting; Endocytosis; G-protein-coupled Receptor (GPCR); Receptor Recycling