ReviewThe EMBO journal2018
Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.
Review in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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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.
The trial behind it
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
192 citing papers in PubMed.
- Anchoring of perforin-2 via the transmembrane domain is required for antigen escape into the cytosol.The EMBO journal · 2026Article
- Alantolactone Activates the Extracellular Signal-Regulated Kinase Signaling Pathway to Promote Tumor Necrosis Factor Receptor 1 Ectodomain Shedding.Molecules (Basel, Switzerland) · 2026Article
- Extracellular matrix and proteolysis: mechanisms driving irreversible changes and shaping cell behavior.The FEBS journal · 2026Review
- Cell-autonomous control of CAR signaling and receptor shedding via ADAM17-mediated proteolysis.Cell · 2026Article
- Activation of the Endothelin System in Chronic Kidney Disease and Kidney Transplant Recipients-Implications for Disease Progression.International journal of molecular sciences · 2026Article
- Transferrin receptor 1 shedding by the pro-inflammatory iRhom-ADAM17 complex and ADAM10 regulates cellular iron uptake and ferroptosis.Experimental & molecular medicine · 2026Article
- Cucurbitacin B Promotes Tumor Necrosis Factor Receptor 1 Ectodomain Shedding by Selectively Activating the Extracellular Signal-Regulated Kinase Signaling Pathway.International journal of molecular sciences · 2026Article
- Structural basis for ADAM17 activation by the iRhom1 pseudoprotease.Cell reports · 2026Article
- Peptides as integrative modulators for clinical prognosis and targeted therapy in pancreatic cancer.Discover oncology · 2026Review
- EctoShed: a novel gene delivery platform for functional analysis of adipocyte-shed proteoforms.BMC research notes · 2026Article
- Clustering hinders APP α-secretase processing in the plasma membrane.Biophysical journal · 2026Article
- Systemic Inflammation Modulates Clearance and Drives Extra-Hepatic Distribution of Extracellular Vesicles.Journal of extracellular vesicles · 2026Article
- Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics.Journal of cellular and molecular medicine · 2026Article
- ADAM10-Mediated Proteolytic Remodelling of Signalling and Adhesion Proteins on Brain Cell-Derived Small Extracellular Vesicles.Journal of extracellular biology · 2026Article
- An Integrative Proteotranscriptomics Approach Reveals New ADAM9 Substrates and Downstream Pathways.Molecular & cellular proteomics : MCP · 2026Article
- Andrographolide targets syndecan4 to impair its interaction with syntenin and inhibits the biogenesis of small extracellular vesicles.The Journal of biological chemistry · 2026Article
- BACE2 tunes lipid uptake through lipid transporters shedding supporting cancer cell proliferation.Journal of experimental & clinical cancer research : CR · 2026Article
- Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- TREM2 and microglial immunity in Alzheimer's disease: mechanisms, genetics, and therapeutic opportunities.Frontiers in immunology · 2026Review
- SPINK3-Sperm Interaction Determines a Stable Sperm Subpopulation With Intact CatSper Channel.Journal of cellular physiology · 2026Article
132 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolytic removal of membrane protein ectodomains (ectodomain shedding) is a post-translational modification that controls levels and function of hundreds of membrane proteins. The contributing proteases, referred to as sheddases, act as important molecular switches in processes ranging from signaling to cell adhesion. When deregulated, ectodomain shedding is linked to pathologies such as inflammation and Alzheimer's disease. While proteases of the "a disintegrin and metalloprotease" (ADAM) and "beta-site APP cleaving enzyme" (BACE) families are widely considered as sheddases, in recent years a much broader range of proteases, including intramembrane and soluble proteases, were shown to catalyze similar cleavage reactions. This review demonstrates that shedding is a fundamental process in cell biology and discusses the current understanding of sheddases and their substrates, molecular mechanisms and cellular localizations, as well as physiological functions of protein ectodomain shedding. Moreover, we provide an operational definition of shedding and highlight recent conceptual advances in the field. While new developments in proteomics facilitate substrate discovery, we expect that shedding is not a rare exception, but rather the rule for many membrane proteins, and that many more interesting shedding functions await discovery.
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