ArticleJournal of cellular and molecular medicine2012
Plasma membrane microdomains regulate TACE-dependent TNFR1 shedding in human endothelial cells.
Article in Journal of cellular and molecular medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 34 citations in OpenAlex.
- Caveolae: Metabolic Platforms at the Crossroads of Health and Disease.International journal of molecular sciences · 2025Review
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- Dermatologic Manifestations of Noninflammasome-Mediated Autoinflammatory Diseases.JID innovations : skin science from molecules to population health · 2023Review
- Tetraspanin 8 Subfamily Members Regulate Substrate-Specificity of a Disintegrin and Metalloprotease 17.Cells · 2022Article
- Endothelial Cell Metabolism in Vascular Functions.Cancers · 2022Review
- Review
- Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions.Biomolecules · 2020Review
- Calcium Mobilization in Endothelial Cell Functions.International journal of molecular sciences · 2019Review
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17.Scientific reports · 2018Article
- Role of Adipose Tissue Endothelial ADAM17 in Age-Related Coronary Microvascular Dysfunction.Arteriosclerosis, thrombosis, and vascular biology · 2017Article
- Proteomic Substrate Identification for Membrane Proteases in the Brain.Frontiers in molecular neuroscience · 2016Review
- Monocyte Tumor Necrosis Factor-α-Converting Enzyme Catalytic Activity and Substrate Shedding in Sepsis and Noninfectious Systemic Inflammation.Critical care medicine · 2015Observational
- Targeting CD13 (aminopeptidase-N) in turn downregulates ADAM17 by internalization in acute myeloid leukaemia cells.Oncotarget · 2014Article
- Caveolin-1 is required for TGF-β-induced transactivation of the EGF receptor pathway in hepatocytes through the activation of the metalloprotease TACE/ADAM17.Cell death & disease · 2014Article
- Article
- Article
- PDK1 decreases TACE-mediated α-secretase activity and promotes disease progression in prion and Alzheimer's diseases.Nature medicine · 2013Article
- Tumour necrosis factor receptor trafficking dysfunction opens the TRAPS door to pro-inflammatory cytokine secretion.Bioscience reports · 2012Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Upon stimulation by histamine, human vascular endothelial cells (EC) shed a soluble form of tumour necrosis factor receptor 1 (sTNFR1) that binds up free TNF, dampening the inflammatory response. Shedding occurs through proteolytic cleavage of plasma membrane-expressed TNFR1 catalysed by TNF-α converting enzyme (TACE). Surface expressed TNFR1 on EC is largely sequestered into specific plasma membrane microdomains, the lipid rafts/caveolae. The purpose of this study was to determine the role of these domains in TACE-mediated TNFR1 shedding in response to histamine. Human umbilical vein endothelial cells derived EA.hy926 cells respond to histamine via H1 receptors to shed TNFR1. Both depletion of cholesterol by methyl-β-cyclodextrin and small interfering RNA knockdown of the scaffolding protein caveolin-1 (cav-1), treatments that disrupt caveolae, reduce histamine-induced shedding of membrane-bound TNFR1. Moreover, immunoblotting of discontinuous sucrose gradient fractions show that TACE, such as TNFR1, is present within low-density membrane fractions, concentrated within caveolae, in unstimulated EA.hy926 endothelial cells and co-immunoprecipitates with cav-1. Silencing of cav-1 reduces the levels of both TACE and TNFR1 protein and displaces TACE, from low-density membrane fractions where TNFR1 remains. In summary, we show that endothelial lipid rafts/caveolae co-localize TACE to surface expressed TNFR1, promoting efficient shedding of sTNFR1 in response to histamine.
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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.