title: The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
abstract: 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.
authors: Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
authors: Laurent
authors: L
authors: Guillemot
authors: Domenica
authors: D
authors: Spadaro
authors: Sandra
authors: S
authors: Citi
mesh_terms: D000818:Animals; D002460:Cell Line; D062446:Claudin-2 / Q000235:genetics / Q000378:metabolism; D062465:Claudin-3 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D062725:Tight Junction Proteins / Q000235:genetics*; D062825:Zonula Occludens Proteins / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D062446:Claudin-2; D062465:Claudin-3; D003598:Cytoskeletal Proteins; D050991:GATA4 Transcription Factor; D008565:Membrane Proteins; D062725:Tight Junction Proteins; D062825:Zonula Occludens Proteins; D020742:rhoA GTP-Binding Protein