The human transmembrane mucin MUC17 responds to TNFα by increased presentation at the plasma membrane

The Biochemical Journal
Hannah SchneiderGunnar C Hansson

Abstract

Transmembrane mucin MUC17 is an integral part of the glycocalyx as it covers the brush border membrane of small intestinal enterocytes and presents an extended O-glycosylated mucin domain to the intestinal lumen. Here, we identified two unknown phosphorylated serine residues, S4428 and S4492, in the cytoplasmic tail of human MUC17. We have previously demonstrated that MUC17 is anchored to the apical membrane domain via an interaction with the scaffolding protein PDZK1. S4492, localized in the C-terminal PDZ binding motif of MUC17, was mutated to generate phosphomimetic and phosphodeficient variants of MUC17. Using Caco-2 cells as a model system, we found that induction of an inflammatory state by long-term stimulation with the proinflammatory cytokine TNFα resulted in an increase of MUC17 protein levels and enhanced insertion of MUC17 and its two phospho-variants into apical membranes. Up-regulation and apical insertion of MUC17 was followed by shedding of MUC17-containing vesicles. Transmembrane mucins have previously been shown to play a role in the prevention of bacterial colonization by acting as sheddable decoys for encroaching bacteria. Overexpression and increased presentation at the plasma membrane of wild-type MUC17 an...Continue Reading

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Citations

Mar 15, 2020·Journal of Cell Science·Thaher Pelaseyed, Gunnar C Hansson
Feb 7, 2020·Journal of Medicinal Chemistry·Maxime LiberelleNicolas Lebègue

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Methods Mentioned

BETA
protein folding
PCR
scraping
FACS
FCS
immunoprecipitation
confocal microscopy

Software Mentioned

Skyline
ImageJ
Imaris
MaxQuant
GraphPad Prism

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