Potent Anti-HIV Chemokine Analogs Direct Post-Endocytic Sorting of CCR5.
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.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva. Geneva, Switzerland.
Claudia
C
Bönsch
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva. Geneva, Switzerland.
Mihaela
M
Munteanu
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva. Geneva, Switzerland.
Irène
I
Rossitto-Borlat
Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Alexandre
A
Fürstenberg
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva. Geneva, Switzerland.
Oliver
O
Hartley
D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D018946:Chemokine CCL5 / Q000008:administration & dosage; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008024:Ligands; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins; D021601:trans-Golgi Network / Q000235:genetics / Q000378:metabolism
C000605253:ARRB1 protein, human; D019390:Arrestins; D018946:Chemokine CCL5; D018925:Chemokines; D008024:Ligands; D019713:Receptors, CCR5; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins