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Tails of the unexpected – an atypical receptor for the chemokine RANTES/CCL5 expressed in brain
Author(s) -
Pease J E
Publication year - 2006
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706910
Subject(s) - chemokine receptor , ccl5 , chemokine , receptor , pertussis toxin , ccr1 , biology , ccr3 , ccr10 , microbiology and biotechnology , chemokine receptor ccr5 , neuroscience , signal transduction , immunology , g protein , genetics , t cell , immune system , il 2 receptor
Chemokines and their receptors play a central role in the trafficking of leukocytes within the body, a process which is amenable to antagonism by small molecules and which holds promise as a treatment for clinically important diseases. In the issue of the British Journal of Pharmacology accompanying this commentary, Ignatov and colleagues describe an unexpected role for the chemokine RANTES/CCL5, namely an ability to signal via the orphan G protein‐coupled receptor named GPR75. This receptor bears little homology to other chemokine receptors, most strikingly within the putative intracellular domains, with the third loop and C‐terminal tail dwarfing those of other known chemokine receptors. This most likely accounts for the atypical pertussis toxin‐insensitive signalling induced by RANTES. Intriguingly, this signalling is neuro‐protective, inducing the survival of a hippocampal cell line following insult with the neurotoxic amyloid‐beta peptide. Since this peptide is implicated in the pathogenesis of Alzheimer's disease, it may be that exploitation of this signalling pathway presents itself as a future therapeutic treatment. British Journal of Pharmacology (2006) 149 , 460–462. doi: 10.1038/sj.bjp.0706910