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

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, FHH...

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Detalles Bibliográficos
Autores principales: Gong, Yongfeng, Renigunta, Vijayaram, Zhou, Yi, Sunq, Abby, Wang, Jinzhi, Yang, Jing, Renigunta, Aparna, Baker, Lane A., Hou, Jianghui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666130/
https://www.ncbi.nlm.nih.gov/pubmed/26446843
http://dx.doi.org/10.1091/mbc.E15-06-0422
Descripción
Sumario: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.