Claudin-4: functional studies beyond the tight junction.

Claudin-4 is an unusual member of the claudin family; in addition to its role in epithelial tight junction barrier function, it is a receptor for the Clostridium perfringens enterotoxin. We have also found that claudin-4 is regulated in mucosal epithelium M cells, both in increased expression of the protein and in redistribution into endocytosis vesicles. Our ongoing studies are studying the potential for developing ligands specific to claudin-4 for targeted delivery of cargo such as proteins and poly(DL-lactide-co-glycolide) nanoparticles to mucosal M cells.

Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery.

Polymer-based microparticles are in clinical use mainly for their ability to provide controlled release of peptides and compounds, but they are also being explored for their potential to deliver vaccines and drugs as suspensions directly into mucosal sites. It is generally assumed that uptake is mediated by epithelial M cells, but this is often not directly measured. To study the potential for optimizing M cell uptake of polymer microparticles in vivo, we produced sub-micron size PLGA particles incorporating a recombinant protein.

Chromosome end protection plasticity revealed by Stn1p and Ten1p bypass of Cdc13p.

Genome stability necessitates a mechanism to protect the termini of linear chromosomes from inappropriate degradation or recombination. In many species this protection depends on 'capping' proteins that bind telomeric DNA. The budding yeast Cdc13p binds single-stranded telomeric sequences, prevents lethal degradation of chromosome ends and regulates telomere extension by telomerase.