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Ann N Y Acad Sci. 2017 Oct;1405(1):102-115. doi: 10.1111/nyas.13393. Epub 2017 Jun 20.

Tight junction strand formation by claudin-10 isoforms and claudin-10a/-10b chimeras.

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Institute of Clinical Physiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Institute of Physiology, Christian-Albrechts-University Kiel, Kiel, Germany.


Claudins are integral components of tight junctions (TJs) in epithelia and endothelia. When expressed in cell lines devoid of TJs, claudins are able to form TJ-like strands at contacts between adjacent cells. According to a current model of TJ strand formation, claudin protomers assemble in an antiparallel double row within the plasma membrane of each cell (cis-interaction) while binding to corresponding double rows from the neighboring cells (trans-interaction). Cis-interaction was proposed to involve two interfaces of the protomers' first extracellular segment (extracellular loop (ECL)1). In the current study, three naturally occurring claudin-10 isoforms and two claudin-10 chimeras were used to investigate strand formation. All constructs were able to interact in cis (Förster/fluorescence resonance energy transfer (FRET)), to integrate into TJs of MDCK-C7 cells (confocal laser scanning microscopy), and to form TJ-like strands in HEK293 cells (freeze-fracture electron microscopy). Strand formation occurred despite the fact that isoform claudin-10a_i1 lacks both structural ECL1 elements reported to be crucial for cis-interaction. Furthermore, results from FRET experiments on claudin-10 chimeras indicated that identity of the first transmembrane region rather than ECL1 is decisive for claudin-10 cis-interaction. Therefore, in addition to the interaction interfaces suggested in the current model for TJ strand assembly, alternative interfaces must exist.


FRET; cis- and trans-interaction; claudin-10 isoforms; freeze-fracture electron microscopy; tight junction strand formation

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