Potent Anti-HIV Chemokine Analogs Direct Post-Endocytic Sorting of CCR5: e0125396

G protein-coupled receptors (GPCRs) are desensitized and internalized following activation. They are then subjected to post-endocytic sorting (degradation, slow recycling or fast recycling). The majority of research on post-endocytic sorting has focused on the role of sequence-encoded address struct...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4)
Main Authors: Bonsch, Claudia, Munteanu, Mihaela, Rossitto-Borlat, Irene, Fuerstenberg, Alexandre, Hartley, Oliver
Format: Article
Language:English
Subjects:
Human immunodeficiency virus
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Summary:G protein-coupled receptors (GPCRs) are desensitized and internalized following activation. They are then subjected to post-endocytic sorting (degradation, slow recycling or fast recycling). The majority of research on post-endocytic sorting has focused on the role of sequence-encoded address structures on receptors. This study focuses on trafficking of CCR5, a GPCR chemokine receptor and the principal entry coreceptor for HIV. Using Chinese Hamster Ovary cells stably expressing CCR5 we show that two different anti-HIV chemokine analogs, PSC-RANTES and 5P14-RANTES, direct receptor trafficking into two distinct subcellular compartments: the trans-Golgi network and the endosome recycling compartment, respectively. Our results indicate that a likely mechanism for ligand-directed sorting of CCR5 involves capacity of the chemokine analogs to elicit the formation of durable complexes of CCR5 and arrestin2 (beta-arrestin-1), with PSC-RANTES eliciting durable association in contrast to 5P14-RANTES, which elicits only transient association.
ISSN:1932-6203
DOI:10.1371/journal.pone.0125396