CRB3 and NF2 orchestrate cytoskeletal dynamics to control epithelial barrier assembly.

ABSTRACT: The gastrointestinal epithelium depends on the apical junctional complex (AJC), composed of tight and adherens junctions, to regulate barrier function. Here, we identify the apical polarity protein Crumbs homolog 3 (CRB3) as an important regulator of AJC assembly and barrier function in intestinal epithelium. Using primary murine colonic epithelial cells (colonoids) from inducible, conditional Crb3-knockout (Crb3ERΔIEC) and control (Crb3fl/fl) mice, we show that CRB3 deficiency compromised barrier function that was associated with a hypercontractile perijunctional actomyosin network and impaired AJC assembly. Loss of CRB3 exacerbated proinflammatory cytokine-induced AJC remodeling, leading to increased intestinal permeability. Crb3ERΔIEC cells exhibited increased RhoA activity and junction

SUBMITTER: Fan S 

PROVIDER: S-EPMC12581665 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature