Signoret, N., Christophe, T., Oppermann, M. and Marsh, M. (2004) pH-independent endocytic cycling of the chemokine receptor CCR5. Traffic, 5 (7). pp. 529-543. ISSN 1398-9219
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 β2-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1β (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-1β dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.
|Institution:||The University of York|
|Academic Units:||The University of York > Hull York Medical School (York)|
|Depositing User:||York RAE Import|
|Date Deposited:||11 Feb 2009 16:12|
|Last Modified:||11 Feb 2009 16:12|