ArticleJournal of molecular cell biology2019
ADAM10 sheddase activation is controlled by cell membrane asymmetry.
Article in Journal of molecular cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed.
- Cell surface remodeling caused by the loss of the flippase subunit TMEM30A in immune cells.Journal of cell science · 2026Article
- Neuroligin-3-CSPG4 interaction maintains oligodendrocyte precursor cell progenitor state and promotes glioma proliferation through mechanotransduction.Nature neuroscience · 2026Article
- Digestive-transformed titanium dioxide nanoparticles disrupt intestinal barrier via mitoxyperilysis mediated by mTOR-cytoskeleton axis dysregulation.Materials today. Bio · 2026Article
- SIRPα Cleavage Is Associated with Inflammatory Response, Corticosteroid Nonresponse, and Worse Prognosis in Clinical and Preclinical Models of Alcohol-Associated Hepatitis.The American journal of pathology · 2026Article
- Lipid-Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mechanoresponsive ion channels Piezo1 and TRPV4 stimulate ADAM10 and ADAM17 with differential impact on endothelial migration and proliferation.Cell communication and signaling : CCS · 2026Article
- Blockade of colon cancer metastasis via single and double silencing ofJournal for immunotherapy of cancer · 2025Article
- Review
- The ectodomain sheddase ADAM10 restricts HIV-1 propagation and is counteracted by Nef.Science advances · 2025Article
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Calcium-sensing receptor- and ADAM10-mediated klotho shedding is regulated by tetraspanin 5.FEBS letters · 2025Article
- Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes.Cell communication and signaling : CCS · 2024Article
- TRPV4 Mediates Alveolar Epithelial Barrier Integrity and Induces ADAM10-Driven E-Cadherin Shedding.Cells · 2024Article
- Overcoming the Tumor Collagen Barriers: A Multistage Drug Delivery Strategy for DDR1-Mediated Resistant Colorectal Cancer Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling.Journal of cell science · 2024Article
- A type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin, membrane-bound and soluble BDCA-2.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Apoptosis-mediated ADAM10 activation removes a mucin barrier promoting T cell efferocytosis.Nature communications · 2024Article
- The matrix metalloproteinase ADAM10 supports hepatitis C virus entry and cell-to-cell spread via its sheddase activity.PLoS pathogens · 2023Article
- Breakdown of Phospholipid Asymmetry Triggers ADAM17-Mediated Rescue Events in Cells Undergoing Apoptosis.Membranes · 2023Article
- Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases.Nature reviews. Molecular cell biology · 2023Review
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of the disintegrin-metalloproteinase ADAM10 may contribute to the development of diseases including tumorigenesis and Alzheimer's disease. The mechanisms underlying ADAM10 sheddase activation are incompletely understood. Here, we show that transient exposure of the negatively charged phospholipid phosphatidylserine (PS) is necessarily required. The soluble PS headgroup was found to act as competitive inhibitor of substrate cleavage. Overexpression of the Ca2+-dependent phospholipid scramblase Anoctamin-6 (ANO6) led to increased PS externalization and substrate release. Transfection with a constitutively active form of ANO6 resulted in maximum sheddase activity in the absence of any stimulus. Calcium-dependent ADAM10 activation could not be induced in lymphocytes of patients with Scott syndrome harbouring a missense mutation in ANO6. A putative PS-binding motif was identified in the conserved stalk region. Replacement of this motif resulted in strong reduction of sheddase activity. In conjunction with the recently described 3D structure of the ADAM10 extracellular domain, a model is advanced to explain how surface-exposed PS triggers ADAM10 sheddase function.
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