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

Dawn Thompson, Simon McArthur, James N Hislop, Roderick J Flower, Mauro Perretti

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Abstract

Formyl-peptide receptor type 2 (FPR2; also called ALX since 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.

Original languageEnglish
Pages (from-to)36166-36178
Number of pages13
JournalThe Journal of Biological Chemistry
Volume289
Early online date17 Oct 2014
DOIs
Publication statusPublished - 26 Dec 2014

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Keywords

  • apoptosis
  • arrestin
  • cell sorting
  • endocytosis
  • G-protein-coupled receptor (GPCR)
  • receptor recycling

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