The mammalian kidney consists of approximately 1–2 million functional units known as nephrons, which can be broadly divided into a glomerulus and a tubule. Blood serum filtration takes place in the glomeruli, whereas the reabsorption of essential biomolecules (e.g., water, salts, sugars, amino acids, etc.) and the associated concentration of primary urine are primarily carried out by the tubular epithelia of the nephron — also referred to as segments.

Although the epithelial cells of different nephron segments vary significantly in their morphology and physiology, they all exhibit pronounced apico-basal cell polarity.

In previous work, we analyzed the role of Pals1 in various renal epithelia. Pals1 (gene: MPP5) interacts with all components of the Crumbs complex through its multiple domains and also mediates interactions between the Crumbs complex and another polarity complex — the aPKC complex.

We were able to show that mice with reduced Pals1 expression in the nephron develop polycystic kidneys and severe proteinuria, indicating defects in tubular epithelia and a compromised renal filtration barrier. These severe impairments are accompanied by alterations in Hippo and TGFβ signaling pathways. This suggests that Pals1 is not only structurally important but also serves as a crucial hub for signal transduction.

This DFG-funded project (DFG WE2550/4-1; project number 414057425)is conducted in close collaboration with the research group of Prof. Michael Krahn (Mecial cell biology, MedD, Münster) and is also part of the DFG Priority Programme “Epithelial Intercellular Junctions as Dynamic Hubs to Integrate Forces, Signals, and Cell Behaviour” (SPP1782)“.