ArticlePloS one2013
The Coxsackievirus and Adenovirus Receptor (CAR) undergoes ectodomain shedding and regulated intramembrane proteolysis (RIP).
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 29 citations in OpenAlex.
- Explorative Insights into Local Immune Response to BK Virus-A Cross-Sectional Study in Urine Samples Between Transplant Recipients and Non-Immunocompromised Hosts.Medicina (Kaunas, Lithuania) · 2026Article
- SARS-CoV-2 Syncytium under the Radar: Molecular Insights of the Spike-Induced Syncytia and Potential Strategies to Limit SARS-CoV-2 Replication.Journal of clinical medicine · 2023Review
- CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis.International journal of molecular sciences · 2023Review
- Increased Circulating Soluble Junctional Adhesion Molecules in Systemic Sclerosis: Association with Peripheral Microvascular Impairment.Life (Basel, Switzerland) · 2022Article
- Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes.Bioengineering (Basel, Switzerland) · 2022Article
- ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion.EMBO reports · 2022Article
- Human Coxsackie- and adenovirus receptor is a putative target of neutrophil elastase-mediated shedding.Molecular biology reports · 2022Article
- MAGI-1 PDZ2 Domain Blockade Averts Adenovirus Infection via Enhanced Proteolysis of the Apical Coxsackievirus and Adenovirus Receptor.Journal of virology · 2021Article
- Soluble JAM-C Ectodomain Serves as the Niche for Adipose-Derived Stromal/Stem Cells.Biomedicines · 2021Article
- Coxsackievirus and Adenovirus Receptor (CXADR): Recent Findings and Its Role and Regulation in Spermatogenesis.Advances in experimental medicine and biology · 2021Review
- Immune Responses to Viral Gene Therapy Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Location of the Cell Adhesion Molecule "Coxsackievirus and Adenovirus Receptor" in the Adult Mouse Brain.Frontiers in neuroanatomy · 2020Article
- Coxsackievirus and adenovirus receptor mediates the responses of endothelial cells to fluid shear stress.Experimental & molecular medicine · 2019Article
- SheddomeDB: the ectodomain shedding database for membrane-bound shed markers.BMC bioinformatics · 2017Review
- Regulation of Alpha-Secretase ADAM10Frontiers in molecular neuroscience · 2017Review
- Coxsackievirus Adenovirus Receptor Loss Impairs Adult Neurogenesis, Synapse Content, and Hippocampus Plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Article
- The Mammalian Blood-Testis Barrier: Its Biology and Regulation.Endocrine reviews · 2015Review
- Principles in the design of ligand-targeted cancer therapeutics and imaging agents.Nature reviews. Drug discovery · 2015Review
- IgLON cell adhesion molecules are shed from the cell surface of cortical neurons to promote neuronal growth.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The Coxsackievirus and Adenovirus Receptor (CAR) is a cell adhesion molecule originally characterized as a virus receptor but subsequently shown to be involved in physiological processes such as neuronal and heart development, epithelial tight junction integrity, and tumour suppression. Proteolysis of cell adhesion molecules and a wide variety of other cell surface proteins serves as a mechanism for protein turnover and, in some cases, cell signaling. Metalloproteases such as A Disintegrin and Metalloprotease (ADAM) family members cleave cell surface receptors to release their substrates' ectodomains, while the presenilin/ɣ-secretase complex mediates regulated intramembrane proteolysis (RIP), releasing intracellular domain fragments from the plasma membrane. In the case of some substrates such as Notch and amyloid precursor protein (APP), the released intracellular domains enter the nucleus to modulate gene expression. We report that CAR ectodomain is constitutively shed from glioma cells and developing neurons, and is also shed when cells are treated with the phorbol ester phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin. We identified ADAM10 as a sheddase of CAR using assays involving shRNA knockdown and rescue, overexpression of wild-type ADAM10 and inhibition of ADAM10 activity by addition of its prodomain. In vitro peptide cleavage, mass spectrometry and mutagenesis revealed the amino acids M224 to L227 of CAR as the site of ADAM10-mediated ectodomain cleavage. CAR also undergoes RIP by the presenilin/γ-secretase complex, and the intracellular domain of CAR enters the nucleus. Ectodomain shedding is a prerequisite for RIP of CAR. Thus, CAR belongs to the increasing list of cell surface molecules that undergo ectodomain shedding and that are substrates for ɣ-secretase-mediated RIP.
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What OpenQuestion holds
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.