ArticlePloS one2012
The PIKfyve inhibitor YM201636 blocks the continuous recycling of the tight junction proteins claudin-1 and claudin-2 in MDCK cells.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Tight junction-high and CDH17-positive cell population is the source of colorectal cancer liver metastases.Nature communications · 2026Article
- Optimizing renal transporter immunodetection: consequences of freeze-thaw during sample preparation.American journal of physiology. Renal physiology · 2024Article
- Article
- Article
- Roles of PIKfyve in multiple cellular pathways.Current opinion in cell biology · 2022Review
- Article
- Endocytosis of Intestinal Tight Junction Proteins: In Time and Space.Inflammatory bowel diseases · 2021Review
- The effects of PIKfyve inhibitor YM201636 on claudins and malignancy potential of nonsmall cell cancer cells.Turkish journal of biology = Turk biyoloji dergisi · 2021Article
- Article
- Epigenetic Regulation of Claudin-1 in the Development of Ovarian Cancer Recurrence and Drug Resistance.Frontiers in oncology · 2021Article
- Immunofluorescent Staining of Claudin-2 in Cultured Kidney Tubular Cells.Bio-protocol · 2020Article
- Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors.Cytotechnology · 2020Article
- Proteoglycan-Dependent Endo-Lysosomal Fusion Affects Intracellular Survival ofFrontiers in immunology · 2020Article
- Claudin-2: Roles beyond Permeability Functions.International journal of molecular sciences · 2019Review
- Newly synthesized claudins but not occludin are added to the basal side of the tight junction.Molecular biology of the cell · 2019Article
- Review
- The JNK signaling pathway plays a key role in methuosis (non-apoptotic cell death) induced by MOMIPP in glioblastoma.BMC cancer · 2019Article
- Brain-derived neurotrophic factor preserves intestinal mucosal barrier function and alters gut microbiota in mice.The Kaohsiung journal of medical sciences · 2018Article
- The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the MgThe Journal of biological chemistry · 2017Article
- Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation.Annals of the New York Academy of Sciences · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Tight junctions mediate the intercellular diffusion barrier found in epithelial tissues but they are not static complexes; instead there is rapid movement of individual proteins within the junctions. In addition some tight junction proteins are continuously being endocytosed and recycled back to the plasma membrane. Understanding the dynamic behaviour of tight junctions is important as they are altered in a range of pathological conditions including cancer and inflammatory bowel disease. In this study we investigate the effect of treating epithelial cells with a small molecule inhibitor (YM201636) of the lipid kinase PIKfyve, a protein which is involved in endocytic trafficking. We show that MDCK cells treated with YM201636 accumulate the tight junction protein claudin-1 intracellularly. In contrast YM201636 did not alter the localization of other junction proteins including ZO-1, occludin and E-cadherin. A biochemical trafficking assay was used to show that YM201636 inhibited the endocytic recycling of claudin-1, providing an explanation for the intracellular accumulation. Claudin-2 was also found to constantly recycle in confluent MDCK cells and treatment with YM201636 blocked this recycling and caused accumulation of intracellular claudin-2. However, claudin-4 showed negligible endocytosis and no detectable intracellular accumulation occurred following treatment with YM201636, suggesting that not all claudins show the same rate of endocytic trafficking. Finally, we show that, consistent with the defects in claudin trafficking, incubation with YM201636 delayed formation of the epithelial permeability barrier. Therefore, YM201636 treatment blocks the continuous recycling of claudin-1/claudin-2 and delays epithelial barrier formation.
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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.