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  • Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6.

Nephrocystin-1 and nephrocystin-4 are required for epithelial morphogenesis and associate with PALS1/PATJ and Par6.

Human molecular genetics (2009-09-17)
Marion Delous, Nathan E Hellman, Helori-Maël Gaudé, Flora Silbermann, André Le Bivic, Rémi Salomon, Corinne Antignac, Sophie Saunier
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Millipore
Glutathione−Agarose, set of 3 pre-packed columns (2.5 ml each), (1:1 suspension in a 0.5 M NaCl + 20% ethanol solution)
Millipore
Glutathione−Agarose, lyophilized powder
Millipore
Protein A–Sepharose® 6MB, aqueous ethanol suspension