دورية أكاديمية
MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C.
| العنوان: | MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C. |
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| المؤلفون: | Segui-Perez C; Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Stapels DAC; Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Ma Z; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.; Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), 138648 Singapore, Singapore.; Department of Pharmacy, National University of Singapore, 117543 Singapore, Singapore., Su J; Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Passchier E; UMAB, Department of Laboratory Pharmacy and Biomedical Genetics, Center for Translational Immunology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands., Westendorp B; Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Wubbolts RW; Department of Biomolecular Health Sciences, Division of Cell Biology, Metabolism and Cancer, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Wu W; Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, the Netherlands.; Singapore Immunology Network (SIgN), Agency for Science, Technology, and Research (A*STAR), 138648 Singapore, Singapore.; Department of Pharmacy, National University of Singapore, 117543 Singapore, Singapore., van Putten JPM; Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands., Strijbis K; Department of Biomolecular Health Sciences, Division of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, the Netherlands. |
| المصدر: | Journal of cell science [J Cell Sci] 2024 Mar 01; Vol. 137 (5). Date of Electronic Publication: 2024 Mar 13. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Company of Biologists Country of Publication: England NLM ID: 0052457 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1477-9137 (Electronic) Linking ISSN: 00219533 NLM ISO Abbreviation: J Cell Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge : Company of Biologists Original Publication: London. |
| مواضيع طبية MeSH: | Tight Junction Proteins*/metabolism , Protein Kinase C*/metabolism, Humans ; Intestines ; Intestinal Mucosa/metabolism ; Tight Junctions/metabolism ; Occludin ; Mucins/metabolism ; Epithelial Cells/metabolism |
| مستخلص: | Glycosylated mucin proteins contribute to the essential barrier function of the intestinal epithelium. The transmembrane mucin MUC13 is an abundant intestinal glycoprotein with important functions for mucosal maintenance that are not yet completely understood. We demonstrate that in human intestinal epithelial monolayers, MUC13 localized to both the apical surface and the tight junction (TJ) region on the lateral membrane. MUC13 deletion resulted in increased transepithelial resistance (TEER) and reduced translocation of small solutes. TEER buildup in ΔMUC13 cells could be prevented by addition of MLCK, ROCK or protein kinase C (PKC) inhibitors. The levels of TJ proteins including claudins and occludin were highly increased in membrane fractions of MUC13 knockout cells. Removal of the MUC13 cytoplasmic tail (CT) also altered TJ composition but did not affect TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC. The responsible PKC member might be PKCδ (or PRKCD) based on elevated protein levels in the absence of full-length MUC13. Our results demonstrate for the first time that a mucin protein can negatively regulate TJ function and stimulate intestinal barrier permeability. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2024. Published by The Company of Biologists Ltd.) |
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| معلومات مُعتمدة: | 91218017 Netherlands ZONMW_ ZonMw; ERC-2019-STG 852452 International ERC_ European Research Council |
| فهرسة مساهمة: | Keywords: Cell-bound mucin; Claudin-1; Claudin-3; Claudin-4; Intestinal barrier function; PRKCD; Paracellular permeability; Tight junctions; Transmembrane mucin |
| المشرفين على المادة: | 0 (Tight Junction Proteins) EC 2.7.11.13 (Protein Kinase C) 0 (Occludin) 0 (Mucins) 0 (MUC13 protein, human) |
| تواريخ الأحداث: | Date Created: 20240212 Date Completed: 20240314 Latest Revision: 20240821 |
| رمز التحديث: | 20240821 |
| مُعرف محوري في PubMed: | PMC10984281 |
| DOI: | 10.1242/jcs.261468 |
| PMID: | 38345099 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1477-9137 |
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| DOI: | 10.1242/jcs.261468 |