ArticleThe Journal of biological chemistry2010
CC chemokine receptor 5 (CCR5) desensitization: cycling receptors accumulate in the trans-Golgi network.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 75 citations in OpenAlex.
- Article
- The beta1-adrenergic receptor in the heart.Cell death discovery · 2025Review
- Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.Nature communications · 2025Article
- Traffic control: Mechanisms of ligand-specific internalization and intracellular distribution of CCR5.Molecular pharmacology · 2025Article
- Arylsulfatases and neuraminidases modulate engagement of CCR5 by chemokines by removing key electrostatic interactions.Scientific reports · 2024Article
- Single-molecule and super-resolved imaging deciphers membrane behavior of onco-immunogenic CCR5.iScience · 2022Article
- Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment.International journal of molecular sciences · 2022Review
- Article
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Metabolic modulation by CDK4/6 inhibitor promotes chemokine-mediated recruitment of T cells into mammary tumors.Cell reports · 2021Article
- Article
- Rapid and low-cost multiplex synthesis of chemokine analogs.The Journal of biological chemistry · 2018Article
- To degrade or not to degrade: mechanisms and significance of endocytic recycling.Nature reviews. Molecular cell biology · 2018Review
- Regulation of C-C chemokine receptor 5 (CCR5) stability by LysThe Journal of biological chemistry · 2018Article
- Differential phosphorylation signals control endocytosis of GPR15.Molecular biology of the cell · 2017Article
- The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection.Frontiers in immunology · 2017Review
- Class B β-arrestin2-dependent CCR5 signalosome retention with natural antibodies to CCR5.Scientific reports · 2016Article
- Downregulation of a GPCR by β-Arrestin2-Mediated Switch from an Endosomal to a TGN Recycling Pathway.Cell reports · 2016Article
- Article
- CCR5 susceptibility to ligand-mediated down-modulation differs between human T lymphocytes and myeloid cells.Journal of leukocyte biology · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
CC chemokine receptor 5 (CCR5), the major HIV coreceptor, is a G protein-coupled receptor (GPCR) involved in cell activation and migration in response to chemokines. Blockade of CCR5 is an effective anti-HIV strategy, and potent anti-HIV chemokine analogs such as PSC-RANTES have been developed. These inhibitors act by interfering with receptor trafficking, thereby inducing prolonged intracellular sequestration of CCR5. Like many GPCRs, CCR5 is desensitized following agonist activation. The initial steps in this process are well understood, but later stages, including where CCR5 is sequestered during desensitization, and how anti-HIV chemokine analogs intervene to achieve prolonged sequestration, have yet to be elucidated in detail. In this study we demonstrate that CCR5 cycles to and from the cell surface via the endosome recycling compartment and the trans-Golgi network during desensitization, accumulating in the trans-Golgi network following internalization by both PSC-RANTES and CCL5, the native ligand from which it was derived. In addition, we show that unlike CCR5 sequestered by CCL5, CCR5 sequestered by PSC-RANTES cannot be induced to return to the cell surface by addition of the small molecule CCR5 inhibitor, TAK-779, and that association of PSC-RANTES with CCR5 is more durable than that of native CCL5 during desensitization. Our findings reconcile the previously conflicting descriptions of the location of sequestered CCR5 during desensitization, as well as providing more general insights into potential trafficking routes for endocytosed GPCRs and further elucidation of the unusual inhibitory mechanism of chemokine analogs with potent anti-HIV activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.