Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney

Abstract The kidney filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened and are surrounded by podocytes, specialized cells that support the glomerular endothelial cells. Mucin-type core 1-derived O-glycans are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1-derived O-glycans is catalyzed by the glycosyltransferase C1galt1. Here, we report that neonatal or adult mice with inducible deletion of C1galt1 exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O-glycans results in altered podocyte foot processes. Further analysis indicated that O-glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process-associated glycoprotein. Our results reveal a new function of O-glycosylation in the integrity of the glomerular filtration barrier.