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

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

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The molecular nature of tight junction architecture and permeability is a longstanding mystery. Here, by comprehensive biochemical, biophysical, genetic, and electron microscopic analyses of claudin-16 and -19 interactions-two claudins that play key poly-genic 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 artifcially 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.

Original languageEnglish
Pages (from-to)4333-4346
Number of pages14
JournalMolecular biology of the cell
Volume26
Issue number24
DOIs
StatePublished - Dec 1 2015

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