A small molecule chaperone rescues keratin-8 mediated trafficking of misfolded podocin to correct genetic Nephrotic Syndrome

Podocin is a key membrane scaffolding protein of the kidney podocyte essential for intact glomerular filtration. Mutations in NPHS2, the podocin-encoding gene, represent the commonest form of inherited nephrotic syndrome (NS), with early, intractable kidney failure. The most frequent podocin gene mutation in European children is R138Q, causing retention of the misfolded protein in the endoplasmic reticulum. Here, we provide evidence that podocin R138Q (but not wild-type podocin) complexes with the intermediate filament protein keratin 8 (K8) thereby preventing its correct trafficking to the plasma membrane.

Source: Kidney International - November 21, 2023 Category: Urology & Nephrology Authors: Valeryia Kuzmuk, Iwona Pranke, Ruth Rollason, Matthew Butler, Wen Y. Ding, Matthew Beesley, Aoife M. Waters, Richard J. Coward, Richard Sessions, Jack Tuffin, Rebecca R. Foster, G éraldine Mollet, Corinne Antignac, Aleksander Edelman, Gavin I. Welsh, Moi Tags: basic research Source Type: research