Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization. Academic Article uri icon


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

published proceedings

  • Mol Biol Cell

altmetric score

  • 0.25

author list (cited authors)

  • Gong, Y., Renigunta, V., Zhou, Y. i., Sunq, A., Wang, J., Yang, J., ... Hou, J.

citation count

  • 58

complete list of authors

  • Gong, Yongfeng||Renigunta, Vijayaram||Zhou, Yi||Sunq, Abby||Wang, Jinzhi||Yang, Jing||Renigunta, Aparna||Baker, Lane A||Hou, Jianghui

editor list (cited editors)

  • Nusrat, A.

publication date

  • December 2015