The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.

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 M...

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Autores principales:	Laurent Guillemot, Domenica Spadaro, Sandra Citi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8e4ab20d256442878aed21d1a8b161af
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spelling	oai:doaj.org-article:8e4ab20d256442878aed21d1a8b161af2021-11-18T07:58:18ZThe junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.1932-620310.1371/journal.pone.0055873https://doaj.org/article/8e4ab20d256442878aed21d1a8b161af2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23409073/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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.Laurent GuillemotDomenica SpadaroSandra CitiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e55873 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laurent Guillemot Domenica Spadaro Sandra Citi The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
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.
format	article
author	Laurent Guillemot Domenica Spadaro Sandra Citi
author_facet	Laurent Guillemot Domenica Spadaro Sandra Citi
author_sort	Laurent Guillemot
title	The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
title_short	The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
title_full	The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
title_fullStr	The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
title_full_unstemmed	The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.
title_sort	junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through gata-4.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/8e4ab20d256442878aed21d1a8b161af
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The junctional proteins cingulin and paracingulin modulate the expression of tight junction protein genes through GATA-4.

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