TY - UNPB
T1 - MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via Protein Kinase C
AU - Segui-Perez, Celia
AU - Stapels, Daphne A.C.
AU - Ma, Ziliang
AU - Su, Jinyi
AU - Passchier, Elsemieke
AU - Westendorp, Bart
AU - Wu, Wei
AU - Putten, Jos P.M. van
AU - Strijbis, Karin
PY - 2022/10/27
Y1 - 2022/10/27
N2 - Regulation and adaptation of intestinal epithelial barrier function is essential for human health. 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 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. 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 result in increased TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC, which is in line with a predicted PKC motif in the MUC13 cytoplasmic tail. The responsible PKC member might be PKCδ based on elevated protein levels in the absence of MUC13. Our results identify MUC13 as a central player in TJ complex stability and intestinal barrier permeability.
AB - Regulation and adaptation of intestinal epithelial barrier function is essential for human health. 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 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. 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 result in increased TEER. The increased buildup of TJ complexes in ΔMUC13 and MUC13-ΔCT cells was dependent on PKC, which is in line with a predicted PKC motif in the MUC13 cytoplasmic tail. The responsible PKC member might be PKCδ based on elevated protein levels in the absence of MUC13. Our results identify MUC13 as a central player in TJ complex stability and intestinal barrier permeability.
U2 - 10.1101/2022.10.27.513982
DO - 10.1101/2022.10.27.513982
M3 - Preprint
SP - 1
EP - 30
BT - MUC13 negatively regulates tight junction proteins and intestinal epithelial barrier integrity via Protein Kinase C
PB - bioRxiv
ER -
