ArticleScientific reports2017
Mechanistic insights into ectodomain shedding: susceptibility of CADM1 adhesion molecule is determined by alternative splicing and O-glycosylation.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- The ADAM Family of Proteases: Structure, Substrates, and Roles in Liver Diseases.International journal of molecular sciences · 2026Review
- Does Podoplanin (PDPN) Reflect the Involvement of the Immunological System in Coronary Artery Disease Risk? A Single-Center Prospective Analysis.International journal of molecular sciences · 2025Article
- UNC5B is an isoform-dependent target for ectodomain shedding.Journal of biochemistry · 2025Article
- Functional Differences Between SIRPα Splice Isoforms.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- ADAM Sheddase Activity Promotes the Detachment of Small Extracellular Vesicles From the Plasma Membrane.Journal of extracellular vesicles · 2025Article
- Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.The Journal of biological chemistry · 2024Article
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- Neuroimmunomodulatory properties of polysialic acid.Glycoconjugate journal · 2023Review
- Article
- Intercellular signaling by ectodomain shedding at the synapse.Trends in neurosciences · 2022Review
- Short-Stalk Isoforms of CADM1 and CADM2 Trigger Neuropathogenic Measles Virus-Mediated Membrane Fusion by Interacting with the Viral Hemagglutinin.Journal of virology · 2022Article
- Members of the Fibroblast Growth Factor Receptor Superfamily Are Proteolytically Cleaved by Two Differently Activated Metalloproteases.International journal of molecular sciences · 2021Article
- Clinical significance of soluble CADM1 as a novel marker for adult T-cell leukemia/lymphoma.Haematologica · 2021Article
- The Role of APPBiomolecules · 2020Review
- To cut or not to cut: New rules for proteolytic shedding of membrane proteins.The Journal of biological chemistry · 2020Article
- Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding.The Journal of biological chemistry · 2020Article
- Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.Cellular and molecular life sciences : CMLS · 2019Review
- Exploratory proteomic analysis implicates the alternative complement cascade in primary CNS vasculitis.Neurology · 2019Article
- TAILS N-terminomics and proteomics reveal complex regulation of proteolytic cleavage byThe Journal of biological chemistry · 2018Article
Corrections and comments
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Authors and funding
11 authors at 8 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ectodomain shedding (shedding) is a post-translational modification, which liberates the extracellular domain of membrane proteins through juxtamembrane processing executed mainly by the ADAM (a disintegrin and metalloprotease) family of metalloproteases. Because shedding alters characteristics of cells in a rapid and irreversible manner, it should be strictly regulated. However, the molecular mechanisms determining membrane protein susceptibility to shedding (shedding susceptibility) are largely unknown. Here we report that alternative splicing can give rise to both shedding-susceptible and shedding-resistant CADM1 (cell adhesion molecule 1) variant proteins. We further show that O-glycans adjacent to the shedding cleavage site interfere with CADM1 shedding, and the only 33-bp alternative exon confers shedding susceptibility to CADM1 by inserting five non-glycosylatable amino acids between interfering O-glycans and the shedding cleavage site. These results demonstrate that shedding susceptibility of membrane protein can be determined at two different levels of its biosynthesis pathway, alternative splicing and O-glycosylation.
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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.