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

Published inPloS one, vol. 10, no. 4, e0125396
Publication date2015
Abstract

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.

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Citation (ISO format)
BOENSCH, Claudia et al. Potent Anti-HIV Chemokine Analogs Direct Post-Endocytic Sorting of CCR5. In: PloS one, 2015, vol. 10, n° 4, p. e0125396. doi: 10.1371/journal.pone.0125396
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ISSN of the journal1932-6203
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