Pals1 haplo-insufficiency in nephrons results in proteinuria and cyst formation

Mammalian nephrons are the physiological subunits of mammalian kidneys which consist of different highly apicobasally polarized epithelial cell types. In epithelial cells polarization is controlled by evolutionary conserved CRB, PAR, or SRIB complexes. Here, we focused on the role of Pals1/Mpp5 in the nephron. Pals1, a core component of the apical membrane determining CRB complex, is highly expressed in renal tubular epithelial and glomerular epithelial cells (podocytes). Surprisingly, haplo-deficient mice, lacking one Pals1/Mpp5 allele in the nephron developed a strong phenotype, accompanied by cyst formation and severe renal filtration barrier defects, which subsequently lead to death after 6-8 weeks. Supporting studies in Drosophila nephrocytes, and epithelial cell culture models elucidated the role of Pals1 as a dose dependent upstream regulator of the crosstalk between Hippo- and TGF-signaling during nephrogenesis.

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Weide T, Vollenbröker B, Schulze U, Djuric I, Edeling M, Bonse J, Hochapfel F, Panichkina O, Wennmann DO, George B, Kim S, Daniel C, Seggewiß J, Amann K, Kriz W, Krahn MP, Pavenstädt H