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Plos One : the Junctional Proteins Cingulin and Paracingulin Modulate the Expression of Tight Junction Protein Genes Through Gata-4, Volume 7

By Koval, Michael

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Book Id: WPLBN0003961193
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : the Junctional Proteins Cingulin and Paracingulin Modulate the Expression of Tight Junction Protein Genes Through Gata-4, Volume 7  
Author: Koval, Michael
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Publication Date:
Publisher: Plos

Description : The cytoplamic junctional proteins cingulin and paracingulin have been implicated in the regulation of gene expression in different cultured cell models. In renal epithelial MDCK cells, depletion of either protein results in a Rho-dependent increase in the expression of claudin-2. Here we examined MDCK cell clones depleted of both cingulin and paracingulin (double-KD cells), and we found that unexpectedly the expression of claudin-2, and also the expression of ZO-3 and claudin-3, were decreased, while RhoA activity was still higher than in control cells. The decreased expression of claudin-2 and other TJ proteins in double–KD cells correlated with reduced levels of the transcription factor GATA-4, and was rescued by overexpression of GATA-4, but not by inhibiting RhoA activity. These results indicate that in MDCK cells GATA-4 is required for the expression of claudin-2 and other TJ proteins, and that maintenance of GATA-4 expression requires either cingulin or paracingulin. These results and previous studies suggest a model whereby cingulin and paracingulin redundantly control the expression of specific TJ proteins through distinct GATA-4- and RhoA-dependent mechanisms, and that in the absence of sufficient levels of GATA-4 the RhoA-mediated upregulation of claudin-2 is inhibited.


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