LAUSR

The central function of renal glomeruli is plasma ultrafiltration for primary urine production. The glomerular filtration barrier consists of a fenestrated endothelium, the glomerular basement membrane and podocytes, mesenchymal-like cells with actin filament-rich protrusions, the "foot processes." Their architecture and function are maintained and regulated by actin and several actin-binding proteins, mutations of which can be causative of glomerular diseases. Since initial immunostaining experiments had demonstrated intense drebrin reactions in renal glomeruli, the distribution of this protein was studied in detail in the kidneys of diverse mammalian species. Double-label confocal laser scanning microscopy revealed drebrin enrichment in mesangial cells of human, bovine, murine, and rat kidneys. In Thy-1.1 nephritic rat glomeruli, the protein was concentrated in mesangial cell processes and upregulated during their formation and remodeling. In adult human and bovine kidneys, drebrin was additionally accumulated in the foot processes of podocytes, a finding confirmed by immunoelectron microscopy. By contrast, podocytes of rodent glomeruli contained significant amounts of drebrin only during early developmental stages. In cultured murine podocytes induced to form cell processes, however, drebrin was concentrated in these protrusions, partly in colocalization with other actin-binding proteins. Protein extracts from human and bovine kidneys comprised 20 S-complexes of drebrin and actin, so-called drebrosomes. In summary, drebrin has to be added to the list of actin-binding proteins regulating actin dynamics of mesangial cell processes and foot processes of podocytes. It will be important to determine its role in hereditary and acquired glomerulopathies.