ArticleAmerican journal of physiology. Cell physiology2013
Claudin-2 pore function requires an intramolecular disulfide bond between two conserved extracellular cysteines.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Claudins proteins in brain tumors: expression patterns and therapeutic target.Biochemia medica · 2026Review
- Biophysics of claudin proteins in tight junction architecture: Three decades of progress.Biophysical journal · 2024Review
- Review
- The role of claudins in homeostasis.Nature reviews. Nephrology · 2023Review
- Molecular mechanism of claudin-15 strand flexibility: A computational study.The Journal of general physiology · 2022Article
- Claudin18.2 is a novel molecular biomarker for tumor-targeted immunotherapy.Biomarker research · 2022Review
- Multiscale modelling of claudin-based assemblies: A magnifying glass for novel structures of biological interfaces.Computational and structural biotechnology journal · 2022Review
- The Sur7 cytoplasmic C terminus regulates morphogenesis and stress responses in Candida albicans.Molecular microbiology · 2021Article
- Chimeric Claudins: A New Tool to Study Tight Junction Structure and Function.International journal of molecular sciences · 2021Article
- Inactivation of paracellular cation-selective claudin-2 channels attenuates immune-mediated experimental colitis in mice.The Journal of clinical investigation · 2020Article
- Drinking and Water Handling in the Medaka Intestine: A Possible Role of Claudin-15 in Paracellular Absorption?International journal of molecular sciences · 2020Article
- Computational Modeling of Claudin Structure and Function.International journal of molecular sciences · 2020Review
- Tight Junctions as Targets and Effectors of Mucosal Immune Homeostasis.Cellular and molecular gastroenterology and hepatology · 2020Review
- Claudin-2: Roles beyond Permeability Functions.International journal of molecular sciences · 2019Review
- Molecular determination of claudin-15 organization and channel selectivity.The Journal of general physiology · 2018Article
- Claudins in morphogenesis: Forming an epithelial tube.Tissue barriers · 2017Review
- Claudin-2-mediated cation and water transport share a common pore.Acta physiologica (Oxford, England) · 2017Article
- One gene, two paracellular ion channels-claudin-10 in the kidney.Pflugers Archiv : European journal of physiology · 2017Review
- Article
- Conceptual barriers to understanding physical barriers.Seminars in cell & developmental biology · 2015Review
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Authors and funding
5 authors at 2 institutions in 1 country.
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Abstract
Claudins constitute a family of tight junction transmembrane proteins whose first extracellular loop (ECL1) determines the paracellular permeability and ion selectivity in epithelia. There are two cysteines in the ECL1 that are conserved among all claudins. We hypothesized that these extracellular cysteines are linked by an intramolecular disulfide bond that is necessary for correct pore folding and function. To test this, we mutated C54 and C64 in claudin-2, either individually or together to alanine or serine, and generated stable Madin-Darby canine kidney (MDCK) I Tet-off cell lines. Immunoblotting showed a higher molecular mass band in the mutants with a single cysteine mutation, consistent with a claudin-2 dimer, suggesting that the two conserved cysteines normally form an intramolecular disulfide bond in wild-type claudin-2. By immunofluorescent staining, the alanine mutants were mislocalized intracellularly, while the serine mutants were expressed at the tight junction. Thus dimerization of both C54A and C64A did not require tight junction expression, suggesting that C54 and C64 are located near an intermolecular interface involved in cis-interaction. The conductance and Na(+) permeability of the serine mutants were markedly lower than the wild type, but there was no difference between the single mutants and the double mutant. We conclude that the disulfide bond between the conserved extracellular cysteines in claudin-2 is necessary for pore formation, probably by stabilizing the ECL1 fold, but is not required for correct protein trafficking. We further speculate that this role is generalizable to other claudin family members.
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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.