DR5 Governs Compound Exocytosis in Colonic Goblet Cells via TATA-Box Binding Protein-Dependent Bestrophin-2 Transcriptional Regulation.

ABSTRACT: The colonic mucus barrier, dependent on goblet cell-secreted mucin2 (Muc2), prevents microbial invasion. Compound exocytosis enables the rapid, high-volume release of mucus from goblet cells; its underlying mechanisms, however, remain unclear. Here, death receptor 5 (DR5) is identified as a critical regulator of this process. Knockout of DR5 exhibits a thinner mucus layer despite elevated Muc2 and enlarged granules, causing mild dysbiosis and enhances susceptibility to Citrobacter rodentium. DR5 knockout and its ligand TRAIL knockdown inhibits carbachol-triggered goblet cell compound exocytosis, while DR5-activator Bioymifi potentiates it. DR5 modulates intracellular pH through the colonic goblet cell-expressed HCO₃ ^- channel Bestrophin-2 (Best2). TRAIL/DR5/Best2 co-l

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12866826 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature