VPS13B, gene responsible for Cohen syndrome, regulates gingival epithelial barrier function via intracellular trafficking of coxsackievirus and adenovirus receptor.

Cohen syndrome is an autosomal recessive genetic disease caused by mutations in the vacuolar protein sorting homolog B (VPS13B) gene that leads to a variety of complications including periodontitis. However, the molecular mechanism underlying periodontal inflammation caused by VPS13B dysfunction in human gingival epithelial cells remains unclear. A previous report noted that coxsackievirus and adenovirus receptor (CXADR) and junctional adhesion molecule 1 (JAM1) are involved in barrier functions against penetration by lipopolysaccharide (LPS) and peptidoglycan (PGN) into gingival tissues. The present study was conducted to examine the effects and significance of VPS13B on gingival barrier function. It was confirmed that loss of VPS13B resulted in decreased cell surface localization of CXADR, but not of JAM1. Additionally, abundant lysosomal localization of CXADR was detected in VPS13B-knockout cells followed treatment with bafilomycin A1, an inhibitor of lysosomal degradation. Other findings indicated that cell-surface localization of the CXADR-chimeric protein, in which C-terminus was exchanged with JAM1, was not disturbed by VPS13B knockout. Finally, VPS13B knockout led to greater permeability of gingival epithelial cell layers and tissues to LPS and PGN, which was restored by increased expression of CXADR-JAM1