ArticleThe Journal of biological chemistry2016
Homodimerization of the Lymph Vessel Endothelial Receptor LYVE-1 through a Redox-labile Disulfide Is Critical for Hyaluronan Binding in Lymphatic Endothelium.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Sliding into Place: The Lymphatic Vessel Endothelial Hyaluronan Receptor LYVE-1 and Its Role as a Mediator of Cell Entry and Trafficking in the Lymphatics.Biomolecules · 2026Review
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- Classification of Protein Disulfide Bonds.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Vascular EC-SOD limits the accumulation, proinflammatory profibrotic reprogramming, and hyaluronan binding of interstitial macrophages in hypoxia.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Structure and unusual binding mechanism of the hyaluronan receptor LYVE-1 mediating leucocyte entry to lymphatics.Nature communications · 2025Article
- Visualizing the Tumor Microenvironment: Molecular Imaging Probes Target Extracellular Matrix, Vascular Networks, and Immunosuppressive Cells.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research.Journal of translational medicine · 2022Article
- Gene expression in meningeal lymphatic endothelial cells following traumatic brain injury in mice.PloS one · 2022Article
- Hyaluronan and Its Receptors: Key Mediators of Immune Cell Entry and Trafficking in the Lymphatic System.Cells · 2021Review
- Dendritic cell entry to lymphatic capillaries is orchestrated by CD44 and the hyaluronan glycocalyx.Life science alliance · 2021Article
- Identification of the hub genes in gastric cancer through weighted gene co-expression network analysis.PeerJ · 2021Article
- Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling.Cells · 2020Review
- The cortical actin network regulates avidity-dependent binding of hyaluronan by the lymphatic vessel endothelial receptor LYVE-1.The Journal of biological chemistry · 2020Article
- The impact of thioredoxin reduction of allosteric disulfide bonds on the therapeutic potential of monoclonal antibodies.The Journal of biological chemistry · 2019Article
- Allosteric disulphide bonds as reversible mechano-sensitive switches that control protein functions in the vasculature.Biophysical reviews · 2019Review
- Allosteric disulfides: Sophisticated molecular structures enabling flexible protein regulation.The Journal of biological chemistry · 2019Review
- Leucocyte Trafficking via the Lymphatic Vasculature- Mechanisms and Consequences.Frontiers in immunology · 2019Review
- Effect of Co-presentation of Adhesive Ligands and Short Hyaluronan on Lymphendothelial Cells.Frontiers in bioengineering and biotechnology · 2018Article
- Application of optical coherence tomography for in vivo monitoring of the meningeal lymphatic vessels during opening of blood-brain barrier: mechanisms of brain clearing.Journal of biomedical optics · 2017Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
The lymphatic vessel endothelial receptor LYVE-1 is implicated in the uptake of hyaluronan (HA) and trafficking of leukocytes to draining lymph nodes. Yet LYVE-1 has only weak affinity for hyaluronan and depends on receptor clustering and higher order ligand organization for durable binding in lymphatic endothelium. An unusual feature of LYVE-1 not found in other HA receptors is the potential to form disulfide-linked homodimers. However, their influence on function has not been investigated. Here we show LYVE-1 homodimers are the predominant configuration in lymphatic endothelium in vitro and in vivo, and formation solely requires the unpaired cysteine residue Cys-201 within the membrane-proximal domain, yielding a 15-fold higher HA binding affinity and an ∼67-fold slower off-rate than the monomer. Moreover, we show non-dimerizing LYVE-1 mutants fail to bind HA even when expressed at high densities in lymphatic endothelial cells or artificially cross-linked with antibody. Consistent with these findings, small angle X-ray scattering (SAXS) indicates the Cys-201 interchain disulfide forms a hinge that maintains the homodimer in an "open scissors" conformation, likely allowing arrangement of the two HA binding domains for mutual engagement with ligand. Finally, we demonstrate the Cys-201 interchain disulfide is highly labile, and selective reduction with TCEP-HCl disrupts LYVE-1 homodimers, ablating HA binding. These findings reveal binding is dependent not just on clustering but also on the biochemical properties of LYVE-1 homodimers. They also mark LYVE-1 as the first Link protein superfamily member requiring covalent homodimerization for function and suggest the interchain disulfide acts as a redox switch in vivo.
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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.