pH-independent endocytic cycling of the chemokine receptor CCR5

N. Signoret; T. Christophe; M. Marsh; M. Oppermann

doi:10.1111/j.1600-0854.2004.00200.x

pH-independent endocytic cycling of the chemokine receptor CCR5

N. Signoret, T. Christophe, M. Marsh, M. Oppermann

The Hull York Medical School

Research output: Contribution to journal › Article › peer-review

Abstract

Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin-coated pits and delivered to recycling endosomes. Subsequently, ligand- free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G-protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well-characterised G protein coupled receptor, the ß2-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1ß (CCL4) only exhibit pH-dependent dissociation at pH <4.0, below the values normally found in endocytic organelles. Although receptor-agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP-1ß dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.

Original language	English
Pages (from-to)	529-543
Number of pages	14
Journal	Traffic
Volume	5
Issue number	7
DOIs	https://doi.org/10.1111/j.1600-0854.2004.00200.x
Publication status	Published - 24 May 2004

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10.1111/j.1600-0854.2004.00200.x

http://dx.doi.org/10.1111/j.1600-0854.2004.00200.x

Cite this

@article{7ae1993cac504f798bc0ea9898a4486d,

title = "pH-independent endocytic cycling of the chemokine receptor CCR5",

abstract = "Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin-coated pits and delivered to recycling endosomes. Subsequently, ligand- free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G-protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well-characterised G protein coupled receptor, the {\ss}2-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1{\ss} (CCL4) only exhibit pH-dependent dissociation at pH <4.0, below the values normally found in endocytic organelles. Although receptor-agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP-1{\ss} dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.",

author = "N. Signoret and T. Christophe and M. Marsh and M. Oppermann",

year = "2004",

month = may,

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doi = "10.1111/j.1600-0854.2004.00200.x",

language = "English",

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pages = "529--543",

journal = "Traffic",

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T1 - pH-independent endocytic cycling of the chemokine receptor CCR5

AU - Signoret, N.

AU - Christophe, T.

AU - Marsh, M.

AU - Oppermann, M.

PY - 2004/5/24

Y1 - 2004/5/24

N2 - Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin-coated pits and delivered to recycling endosomes. Subsequently, ligand- free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G-protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well-characterised G protein coupled receptor, the ß2-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1ß (CCL4) only exhibit pH-dependent dissociation at pH <4.0, below the values normally found in endocytic organelles. Although receptor-agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP-1ß dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.

AB - Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin-coated pits and delivered to recycling endosomes. Subsequently, ligand- free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G-protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well-characterised G protein coupled receptor, the ß2-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1ß (CCL4) only exhibit pH-dependent dissociation at pH <4.0, below the values normally found in endocytic organelles. Although receptor-agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP-1ß dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.

U2 - 10.1111/j.1600-0854.2004.00200.x

DO - 10.1111/j.1600-0854.2004.00200.x

M3 - Article

SN - 1398-9219

VL - 5

SP - 529

EP - 543

JO - Traffic

JF - Traffic

IS - 7

ER -