In the November 15 issue of the Journal of Clinical Investigation, Karl Tryggvason and colleagues from the Karolinska Institute used electron tomography to obtain detailed images of the SD that were previously impossible to obtain. They found that some elements of the proposed zipper-like structure hold true but the pores of this filtration structure appear to be more irregularly shaped that previously proposed. The authors also demonstrated a crucial role for the protein nephrin, expressed by the podocytes and localized in the area of the SD, in the formation of this structure. Indeed, the fibers that constitute the SD appear to be formed largely by the association of extracellular nephrin strands. The authors examined a Finnish population of individuals lacking the nephrin protein due to a mutation in then nephrin gene, and also examined nephrin-deficient mice and found that in all cases the ordered SD structure was no longer evident and excessive protein levels were found in the urine.
In an accompanying commentary, William M. Deen from the Massachusetts Institute of Technology, discusses how the many parts of the glomerular capillary wall function to determine the permeability of this living ultrafiltration membrane.
TITLE: Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography.