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First published online March 5, 2008

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G12 breaks up the party

Understanding the regulation and assembly of tight junctions (TJs) is crucial for understanding how epithelial cells form and maintain their polarity, but the mechanisms are poorly defined. In this report, Bradley M. Denker and colleagues (p. 814) investigate the potential role of the G protein subunit G12 in regulating TJ assembly in MDCK monolayers. G proteins have been implicated in the regulation of barrier function and TJ assembly, and G subunits have been shown to localise to epithelial-cell TJs. The authors previously showed that G12 directly interacts with ZO-1, one of the scaffolding proteins of the TJ. Here, they show that G12 activation stimulates phosphorylation of ZO-1 and ZO-2 by Src in an Hsp90-dependent manner, leading to dissociation of occludin and claudin-1 from the ZO-1 protein complex, and disruption of TJ integrity. These effects can be blocked by the Src-kinase inhibitor PP2 and the Hsp90 inhibitor geldanamycin. Thrombin (a known agonist for G12/G13-coupled pathways), acting through G12, slows the assembly of TJs. This study provides the first evidence that G12 is a negative regulator of TJ assembly.

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G12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly

Ernesto Sabath, Hideyuki Negoro, Sarah Beaudry, Manuel Paniagua, Susanne Angelow, Jagesh Shah, Nicholas Grammatikakis, Alan S. L. Yu, and Bradley M. Denker
JCS 2008 121: 814-824. [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?