MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C

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MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C
Title:
MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C
Journal Title:
Journal of Cell Science
Keywords:
Publication Date:
12 February 2024
Citation:
Segui-Perez, C., Stapels, D. A. C., Ma, Z., Su, J., Passchier, E., Westendorp, B., Wubbolts, R. W., Wu, W., van Putten, J. P. M., & Strijbis, K. (2024). MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via protein kinase C. Journal of Cell Science, 137(5). https://doi.org/10.1242/jcs.261468
Abstract:
ABSTRACT 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.
License type:
Attribution 4.0 International (CC BY 4.0)
Funding Info:
There was no specific funding for the research done
Description:
ISSN:
1477-9137
0021-9533
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