ArticleMolecular and cellular biology2006
Role of the Cldn6 cytoplasmic tail domain in membrane targeting and epidermal differentiation in vivo.
Article in Molecular and cellular biology, 2006. 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.
- Biophysics of claudin proteins in tight junction architecture: Three decades of progress.Biophysical journal · 2024Review
- Knockdown of CLAUDIN-6 Inhibited Apoptosis and Induced Proliferation of Bovine Cumulus Cells.International journal of molecular sciences · 2022Article
- CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers.International journal of molecular sciences · 2021Review
- The blood-brain and gut-vascular barriers: from the perspective of claudins.Tissue barriers · 2021Review
- A SUMOylation-dependent HIF-1α/CLDN6 negative feedback mitigates hypoxia-induced breast cancer metastasis.Journal of experimental & clinical cancer research : CR · 2020Article
- Self-organizing neuruloids model developmental aspects of Huntington's disease in the ectodermal compartment.Nature biotechnology · 2019Article
- Expression of CLDN6 in tissues of gastric cancer patients: Association with clinical pathology and prognosis.Oncology letters · 2019Article
- CLDN6 enhances chemoresistance to ADM via AF-6/ERKs pathway in TNBC cell line MDAMB231.Molecular and cellular biochemistry · 2018Article
- Prognostic significance of claudin-1 and cyclin B1 protein expression in patients with hypopharyngeal squamous cell carcinoma.Oncology letters · 2016Article
- Systems Proteomics View of the Endogenous Human Claudin Protein Family.Journal of proteome research · 2016Review
- Transcriptome Analysis of HepG2 Cells Expressing ORF3 from Swine Hepatitis E Virus to Determine the Effects of ORF3 on Host Cells.BioMed research international · 2016Article
- Emerging multifunctional roles of Claudin tight junction proteins in bone.Endocrinology · 2014Review
- Developmental lung expression and transcriptional regulation of claudin-6 by TTF-1, Gata-6, and FoxA2.Respiratory research · 2014Article
- Regulation of claudins in blood-tissue barriers under physiological and pathological states.Tissue barriers · 2013Review
- Claudins and the modulation of tight junction permeability.Physiological reviews · 2013Review
- Mechanisms that determine the internal environment of the developing brain: a transcriptomic, functional and ultrastructural approach.PloS one · 2013Article
- Transgene-mediated rescue of spermatogenesis in Cldn11-null mice.Biology of reproduction · 2012Article
- Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis.Nature reviews. Molecular cell biology · 2011Review
- Article
- Genetic targeting of the endoderm with claudin-6CreER.Developmental dynamics : an official publication of the American Association of Anatomists · 2008Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is widely recognized that the claudin (Cldn) family of four tetraspan transmembrane proteins is crucial for tight junction assembly and permeability barrier function; however, the precise role of the tail and loop domains in Cldn function is not understood. We hypothesized that the cytoplasmic tail domain of Cldn6 is crucial for membrane targeting and hence epidermal permeability barrier (EPB) formation. To test this hypothesis via a structure-function approach, we generated a tail deletion of Cldn6 (CDelta187) and evaluated its role in epidermal differentiation and EPB formation through its forced expression via the involucrin (Inv) promoter in the suprabasal compartment of the transgenic mouse epidermis. Even though a functional barrier formed, Inv-CDelta187 mice displayed histological and biochemical abnormalities in the epidermal differentiation program and stimulation of epidermal cell proliferation in both the basal and suprabasal compartments of the interfolliclar epidermis, leading to a thickening of the epidermis after 1 week of age that persisted throughout life. Although some membrane localization was evident, our studies also revealed a significant amount of not only Cldn6 but also Cldn10, Cldn11, and Cldn18 in the cytoplasm of transgenic epidermal cells as well as the activation of a protein-unfolding pathway. These findings demonstrate that the overexpression of a tail truncation mutant of Cldn6 mislocalizes Cldn6 and other Cldn proteins to the cytoplasm and triggers a postnatal increase in proliferation and aberrant differentiation of the epidermis, emphasizing the importance of the Cldn tail domain in membrane targeting and function in vivo.
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