ArticleProceedings of the National Academy of Sciences of the United States of America2015
Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 67 citations in OpenAlex.
- Molecular Boolean analyses of chemokine (C-C motif) receptor 1, αBiochemistry and biophysics reports · 2026Article
- Effects of Blood Pressure and Antihypertensive Drugs on Rheumatoid Arthritis: A Mendelian Randomization, Network Pharmacology, and Experimental Validation.International journal of general medicine · 2026Article
- GPCR Heterodimers: Implications for Biased Signaling.Handbook of experimental pharmacology · 2026Review
- Activation of Chemokine (C-C Motif) Receptor 1 Modulates αJournal of the American Heart Association · 2025Article
- Modulation of neuronal α1-adrenergic receptor reduces tauopathy and neuroinflammation by inhibiting the STING/NF-κB/NLRP3 signaling pathway in Alzheimer's disease mice.Journal of neuroinflammation · 2025Article
- Transcriptomic signatures of cold acclimated adipocytes reveal CXCL12 as a Brown autocrine and paracrine chemokine.Molecular metabolism · 2025Article
- Chemokine receptor hetero-oligomers regulate monocyte chemotaxis.Life science alliance · 2024Article
- LPA1-mediated inhibition of CXCR4 attenuates CXCL12-induced signaling and cell migration.Cell communication and signaling : CCS · 2023Article
- G protein activation via chemokine (C-X-C motif) receptor 4 and αFEBS letters · 2023Article
- αPharmacological research · 2023Article
- DPP4-Truncated CXCL12 Alters CXCR4/ACKR3 Signaling, Osteogenic Cell Differentiation, Migration, and Senescence.ACS pharmacology & translational science · 2023Article
- Heteromerization between αFEBS letters · 2022Article
- αProceedings of the National Academy of Sciences of the United States of America · 2022Article
- CXCR4/CXCL12 Activities in the Tumor Microenvironment and Implications for Tumor Immunotherapy.Cancers · 2022Review
- The Chemokine (C-C Motif) Receptor 2 Antagonist INCB3284 Reduces Fluid Requirements and Protects From Hemodynamic Decompensation During Resuscitation From Hemorrhagic Shock.Critical care explorations · 2022Article
- Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing.Cytogenetic and genome research · 2022Article
- Class A G protein-coupled receptors assemble into functional higher-order hetero-oligomers.FEBS letters · 2021Article
- Chemokine receptor antagonists with αJournal of basic and clinical physiology and pharmacology · 2021Article
- Design and Generation of Self-Assembling Peptide Virus-like Particles with Intrinsic GPCR Inhibitory Activity.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Plasticity of seven-transmembrane-helix receptor heteromers in human vascular smooth muscle cells.PloS one · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Recent evidence suggests that chemokine (C-X-C motif) receptor 4 (CXCR4) contributes to the regulation of blood pressure through interactions with α1-adrenergic receptors (ARs) in vascular smooth muscle. The underlying molecular mechanisms, however, are unknown. Using proximity ligation assays to visualize single-molecule interactions, we detected that α1A/B-ARs associate with CXCR4 on the cell surface of rat and human vascular smooth muscle cells (VSMC). Furthermore, α1A/B-AR could be coimmunoprecipitated with CXCR4 in a HeLa expression system and in human VSMC. A peptide derived from the second transmembrane helix of CXCR4 induced chemical shift changes in the NMR spectrum of CXCR4 in membranes, disturbed the association between α1A/B-AR and CXCR4, and inhibited Ca(2+) mobilization, myosin light chain (MLC) 2 phosphorylation, and contraction of VSMC upon α1-AR activation. CXCR4 silencing reduced α1A/B-AR:CXCR4 heteromeric complexes in VSMC and abolished phenylephrine-induced Ca(2+) fluxes and MLC2 phosphorylation. Treatment of rats with CXCR4 agonists (CXCL12, ubiquitin) reduced the EC50 of the phenylephrine-induced blood pressure response three- to fourfold. These observations suggest that disruption of the quaternary structure of α1A/B-AR:CXCR4 heteromeric complexes by targeting transmembrane helix 2 of CXCR4 and depletion of the heteromeric receptor complexes by CXCR4 knockdown inhibit α1-AR-mediated function in VSMC and that activation of CXCR4 enhances the potency of α1-AR agonists. Our findings extend the current understanding of the molecular mechanisms regulating α1-AR and provide an example of the importance of G protein-coupled receptor (GPCR) heteromerization for GPCR function. Compounds targeting the α1A/B-AR:CXCR4 interaction could provide an alternative pharmacological approach to modulate blood pressure.
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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.