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Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6
Nephronophthisis (NPH) is an autosomal recessive disorder characterized by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end-stage renal failure. The disease is caused by mutations in NPHP1-9 genes, which encode the nephrocystins, proteins locali...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778369/ https://www.ncbi.nlm.nih.gov/pubmed/19755384 http://dx.doi.org/10.1093/hmg/ddp434 |
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author | Delous, Marion Hellman, Nathan E. Gaudé, Helori-Maël Silbermann, Flora Le Bivic, André Salomon, Rémi Antignac, Corinne Saunier, Sophie |
author_facet | Delous, Marion Hellman, Nathan E. Gaudé, Helori-Maël Silbermann, Flora Le Bivic, André Salomon, Rémi Antignac, Corinne Saunier, Sophie |
author_sort | Delous, Marion |
collection | PubMed |
description | Nephronophthisis (NPH) is an autosomal recessive disorder characterized by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end-stage renal failure. The disease is caused by mutations in NPHP1-9 genes, which encode the nephrocystins, proteins localized to cell–cell junctions and centrosome/primary cilia. Here, we show that nephrocystin mRNA expression is dramatically increased during cell polarization, and shRNA-mediated knockdown of either NPHP1 or NPHP4 in MDCK cells resulted in delayed tight junction (TJ) formation, abnormal cilia formation and disorganized multi-lumen structures when grown in a three-dimensional collagen matrix. Some of these phenotypes are similar to those reported for cells depleted of the TJ proteins PALS1 or Par3, and interestingly, we demonstrate a physical interaction between these nephrocystins and PALS1 as well as their partners PATJ and Par6 and show their partial co-localization in human renal tubules. Taken together, these results demonstrate that the nephrocystins play an essential role in epithelial cell organization, suggesting a plausible mechanism by which the in vivo histopathologic features of NPH might develop. |
format | Text |
id | pubmed-2778369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27783692009-11-18 Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 Delous, Marion Hellman, Nathan E. Gaudé, Helori-Maël Silbermann, Flora Le Bivic, André Salomon, Rémi Antignac, Corinne Saunier, Sophie Hum Mol Genet Articles Nephronophthisis (NPH) is an autosomal recessive disorder characterized by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end-stage renal failure. The disease is caused by mutations in NPHP1-9 genes, which encode the nephrocystins, proteins localized to cell–cell junctions and centrosome/primary cilia. Here, we show that nephrocystin mRNA expression is dramatically increased during cell polarization, and shRNA-mediated knockdown of either NPHP1 or NPHP4 in MDCK cells resulted in delayed tight junction (TJ) formation, abnormal cilia formation and disorganized multi-lumen structures when grown in a three-dimensional collagen matrix. Some of these phenotypes are similar to those reported for cells depleted of the TJ proteins PALS1 or Par3, and interestingly, we demonstrate a physical interaction between these nephrocystins and PALS1 as well as their partners PATJ and Par6 and show their partial co-localization in human renal tubules. Taken together, these results demonstrate that the nephrocystins play an essential role in epithelial cell organization, suggesting a plausible mechanism by which the in vivo histopathologic features of NPH might develop. Oxford University Press 2009-12-15 2009-09-14 /pmc/articles/PMC2778369/ /pubmed/19755384 http://dx.doi.org/10.1093/hmg/ddp434 Text en © The Author 2009. Published by Oxford University Press http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Delous, Marion Hellman, Nathan E. Gaudé, Helori-Maël Silbermann, Flora Le Bivic, André Salomon, Rémi Antignac, Corinne Saunier, Sophie Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title | Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title_full | Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title_fullStr | Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title_full_unstemmed | Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title_short | Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6 |
title_sort | nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with pals1/patj and par6 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778369/ https://www.ncbi.nlm.nih.gov/pubmed/19755384 http://dx.doi.org/10.1093/hmg/ddp434 |
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