The glomerular filtration barrier

Blood enters the glomerular capillaries and is filtered across the endothelium and the glomerular basement membrane and through the filtration slits between podocyte foot processes to produce the primary urine filtrate. In healthy glomeruli, this barrier restricts the passage of macromolecules. CatL, the expression of which is increased in human proteinuric diseases and in an LPS-induced mouse model of proteinuria, causes proteinuria and foot process effacement through cleavage of the GTPase dynamin, an actin-binding protein. The same effects are induced by gene delivery into mice of dynK44A—a mutant form of dynamin that does not bind GTP—or of the CatL-cleaved product of dynamin (p40). Conversely, gene delivery into proteinuric mice of dynL356Q and dynR725A, two CatL-resistant dynamin mutants, reverses proteinuria and foot process effacement.