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First published online July 25, 2006

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SURfing through tight junctions

Small molecules cross epithelia by passing through or between cells. Molecules following the latter, paracellular, route must pass through tight junctions, the permeability of which is tightly regulated. Now, Thomas Jöns and co-authors report that K⁺-ATP ion channels help to regulate tight junction permeability (see p. 3087). K⁺-ATP channels contain Kir6 K⁺ channels and sulphonylurea receptor (SUR) subunits. These have ATPase activity and, like other ATP-binding cassette (ABC) proteins, alter the activity of associated proteins by acting as mechanochemical devices. The authors show that Kir6.1 and SUR2A localize to regulated tight junctions (e.g. those in intestines), but not to non-regulated tight junctions, and coimmunoprecipitate with tight junction proteins. They also report that the permeability of tight junctions is affected by agents that alter Kir6.1 and SUR2A function. In particular, tolbutamide, which interacts with SUR2A, increases paracellular permeability, thus explaining why this anti-diabetic drug often causes diarrhoea. These findings indicate that Kir6-SUR complexes are important regulators of paracellular permeability and also provide a basis for the development of improved anti-diabetic drugs.

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Related articles in JCS:

K⁺-ATP-channel-related protein complexes: potential transducers in the regulation of epithelial tight junction permeability

Thomas Jöns, Daniel Wittschieber, Anja Beyer, Carola Meier, Andreas Brune, Achim Thomzig, Gudrun Ahnert-Hilger, and Rüdiger W. Veh
JCS 2006 119: 3087-3097. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?