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

doi:10.1074/jbc.M114.612630

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

Medical Sciences

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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 language	English
Pages (from-to)	36166-36178
Number of pages	13
Journal	The Journal of Biological Chemistry
Volume	289
Early online date	17 Oct 2014
DOIs	https://doi.org/10.1074/jbc.M114.612630
Publication status	Published - 26 Dec 2014

Bibliographical note

Copyright © 2014, The American Society for Biochemistry and Molecular Biology.

Free via Open Access: OA Free via Creative Commons: CC

This work was funded by the Wellcome Trust (Program Grant 08667/Z/08/
Z), The Friends of Anchor Trust (Grant BM114 RGB4561) and, in part by the
University of Aberdeen.

Keywords

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

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10.1074/jbc.M114.612630

Identification of a Novel Recycling Sequence in the C-tail of
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/3.0/
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title = "Identification of a novel recycling sequence in the C-tail of FPR2/ALX: association with cell protection from apoptosis",

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.",

keywords = "apoptosis, arrestin, cell sorting, endocytosis, G-protein-coupled receptor (GPCR), receptor recycling",

author = "Dawn Thompson and Simon McArthur and Hislop, {James N} and Flower, {Roderick J} and Mauro Perretti",

note = "Copyright {\textcopyright} 2014, The American Society for Biochemistry and Molecular Biology. Free via Open Access: OA Free via Creative Commons: CC This work was funded by the Wellcome Trust (Program Grant 08667/Z/08/ Z), The Friends of Anchor Trust (Grant BM114 RGB4561) and, in part by the University of Aberdeen.",

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doi = "10.1074/jbc.M114.612630",

language = "English",

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AU - Thompson, Dawn

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AU - Hislop, James N

AU - Flower, Roderick J

AU - Perretti, Mauro

N1 - Copyright © 2014, The American Society for Biochemistry and Molecular Biology. Free via Open Access: OA Free via Creative Commons: CC This work was funded by the Wellcome Trust (Program Grant 08667/Z/08/ Z), The Friends of Anchor Trust (Grant BM114 RGB4561) and, in part by the University of Aberdeen.

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Y1 - 2014/12/26

N2 - 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.

AB - 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.

KW - apoptosis

KW - arrestin

KW - cell sorting

KW - endocytosis

KW - G-protein-coupled receptor (GPCR)

KW - receptor recycling

U2 - 10.1074/jbc.M114.612630

DO - 10.1074/jbc.M114.612630

M3 - Article

C2 - 25326384

SN - 0021-9258

VL - 289

SP - 36166

EP - 36178

JO - The Journal of Biological Chemistry

JF - The Journal of Biological Chemistry

ER -

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

Abstract

Bibliographical note

Keywords

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James Hislop

Dawn Thompson

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

Abstract

Bibliographical note

Keywords

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Fingerprint

Profiles

James Hislop

Dawn Thompson

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