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Differential Trafficking of the FPR2/ALX receptor in response to endogenous or synthetic ligands
Author(s) -
Thompson Dawn,
Perretti Mauro
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.649.9
Subject(s) - endocytosis , agonist , endocytic cycle , microbiology and biotechnology , receptor , chemistry , g protein coupled receptor , endogenous agonist , phosphorylation , mapk/erk pathway , biochemistry , biology , dopamine receptor d1
Following agonist activation G protein‐coupled receptors (GPCR) undergo rapid endocytosis and are recycled back to the cell surface to once again bind agonist (resensitisation), or targeted to the lysosomes (downregulation). The formyl peptide family (comprising FPR1, FPR2/ALX and FPR3) regulate both pro and anti‐inflammatory effectors in the immune response. Despite several articles identifying important phosphorylation residues, little is known about the endocytosis and subsequent post‐endocytic sorting of these receptors. Here we compare the trafficking and signalling of FPR2 in response to synthetic or endogenous agonists. The synthetic peptide (500nM WKYMWm) induced rapid endocytosis of FPR2 followed by extensive recycling after agonist washout. Furthermore, FPR2 was stable following prolonged agonist treatment (180mins). Consistent with recycling, ERK phosphorylation was desensitised after 30mins agonist treatment but recovered after agonist washout. In contrast, neither the endogenous anti‐inflammatory Annexin A1 nor the pro‐inflammatory Serum Amyloid A (SAA) induced endocytosis of the receptor, despite robust ERK phosphorylation and calcium release. These findings have profound implications for the design of new ligands to treat inflammatory disorders, since use of synthetic ligands promoting endocytosis may help reset the system returning signalling to a physiological level.