Nephrotic Syndrome, FSGS, Glomerulonephritis:

Podocytes and Slit Diaphragm Signaling in Glomerular Diseases

Diseases of the kidney filtration barrier (e.g. FSGS or other types of glomerulonephritis) are a leading cause of chronic kidney disease and endstage renal failure. The human kidney filters about 180 Liters of primary urine per day which is basically free of proteins. Filtration takes place in a million mini filter units called glomeruli. The filter that is responsible for the enormous filtration function of glomeruli consists of three layers, the glomerular endothelium, the basement membrane and podocytes, the visceral epithelial cells of the renal glomerulus.

The terminally differentiated and highly specialized podocytes are required for integrity and function of the kidney filtration barrier. Podocytes are characterized by their complex architecture with interdigitating foot processes. These processes are connected by a highly specialized cell junction called the slit diaphragm.

We have demonstrated that signaling at the slit diaphragm is of central importance for the survival of podocytes and for the function of the glomerular filtration barrier. We are currently using conditional knock-out mouse models as well as C. elegans and Drosophila to address the function of podocyte and slit diaphragm proteins. Some of these proteins are conserved in evolution and, in addition to serving as essential proteins at the renal filtration barrier, act as guidance signals in synaptogenesis or are instrumental for the proper development of the fly eye.