ArticleThe Journal of biological chemistry2010
The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction.
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 129 papers.
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Who cites it
129 citing papers in PubMed, 248 citations in OpenAlex.
- Sitagliptin Modulates Functional and Phenotypic Properties of Human Neutrophils Under Normal- and High-Glucose Conditions In Vitro.Molecules (Basel, Switzerland) · 2026Article
- Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction.Cell discovery · 2026Article
- High throughput mutational characterization of the GPCR ligand C5a using yeast display and deep sequencing.Structure (London, England : 1993) · 2026Article
- The Pleiotropic Effect of Complement C5a-C5aR1 Pathway in Diseases: From Immune Regulation to Targeted Therapy.International journal of molecular sciences · 2025Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Action of the Terminal Complement Pathway on Cell Membranes.The Journal of membrane biology · 2025Review
- Advances in the treatment of ANCA-associated vasculitis.Nature reviews. Rheumatology · 2025Review
- Friend or foe: assessing the value of animal models for facilitating clinical breakthroughs in complement research.The Journal of clinical investigation · 2025Review
- Complement's involvement in allergic Th2 immunity: a cross-barrier perspective.The Journal of clinical investigation · 2025Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Staphylococcal toxin PVL ruptures model membranes under acidic conditions through interactions with cardiolipin and phosphatidic acid.PLoS biology · 2025Article
- Article
- C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.Investigative ophthalmology & visual science · 2025Article
- The Complement System.Advances in experimental medicine and biology · 2025Review
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Article
- Article
- The Complement System and C4b-Binding Protein: A Focus on the Promise of C4BPα as a Biomarker to Predict Clopidogrel Resistance.Molecular diagnosis & therapy · 2024Review
- Cell-intrinsic C5a synergizes with Dectin-1 in macrophages to mediate fungal killing.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- C5aR2 Deficiency Lessens C5aR1 Distribution and Expression in Neutrophils and Macrophages.Journal of immunology research · 2024Article
69 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The complement anaphylatoxin C5a is a proinflammatory component of host defense that functions through two identified receptors, C5a receptor (C5aR) and C5L2. C5aR is a classical G protein-coupled receptor, whereas C5L2 is structurally homologous but deficient in G protein coupling. In human neutrophils, we show C5L2 is predominantly intracellular, whereas C5aR is expressed on the plasma membrane. Confocal analysis shows internalized C5aR following ligand binding is co-localized with both C5L2 and beta-arrestin. Antibody blockade of C5L2 results in a dramatic increase in C5a-mediated chemotaxis and ERK1/2 phosphorylation but does not alter C5a-mediated calcium mobilization, supporting its role in modulation of the beta-arrestin pathway. Association of C5L2 with beta-arrestin is confirmed by cellular co-immunoprecipitation assays. C5L2 blockade also has no effect on ligand uptake or C5aR endocytosis in human polymorphonuclear leukocytes, distinguishing its role from that of a rapid recycling or scavenging receptor in this cell type. This is thus the first example of a naturally occurring seven-transmembrane segment receptor that is both obligately uncoupled from G proteins and a negative modulator of signal transduction through the beta-arrestin pathway. Physiologically, these properties provide the possibility for additional fine-tuning of host defense.
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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.