Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization

• DOI: 10.1091/mbc.e15-06-0422
• Publication Date: 2015-10-08T02:37:56Z
• Authors: Yongfeng Gong; Vijayaram Renigunta; Yi Zhou; Abby Sunq; Jinzhi Wang; Jing Yang; Aparna Renigunta; Lane A. Baker; Jianghui Hou
• Keywords: Claudin; Occludin; Septate junctions

The molecular nature of tight junction architecture and permeability is a long-standing mystery. Here, by comprehensive biochemical, biophysical, genetic, electron microscopic analyses claudin-16 -19 interactions--two claudins that play key polygenic roles in fatal human renal disease, FHHNC--we found 1) form stable dimer through cis association transmembrane domains 3 4; 2) mutations disrupting the interaction increase ultrastructural complexity but reduce permeability; 3) no claudin hemichannel or heterotypic channel made trans can exist. These principles be used to artificially alter permeabilities various epithelia manipulating selective interactions. Our study also emphasizes use novel recording approach based on scanning ion conductance microscopy resolve with submicrometer precision.