First published December 15, 2004 - More info
Nephrin is a key functional component of the slit diaphragm, the structurally unresolved molecular filter in renal glomerular capillaries. Abnormal nephrin or its absence results in severe proteinuria and loss of the slit diaphragm. The diaphragm is a thin extracellular membrane spanning the approximately 40-nm-wide filtration slit between podocyte foot processes covering the capillary surface. Using electron tomography, we show that the slit diaphragm comprises a network of winding molecular strands with pores the same size as or smaller than albumin molecules, as demonstrated in humans, rats, and mice. In the network, which is occasionally stratified, immunogold-nephrin antibodies labeled individually detectable globular cross strands, about 35 nm in length, lining the lateral elongated pores. The cross strands, emanating from both sides of the slit, contacted at the slit center but had free distal endings. Shorter strands associated with the cross strands were observed at their base. Immunolabeling of recombinant nephrin molecules on transfected cells and in vitrified solution corroborated the findings in kidney. Nephrin-deficient proteinuric patients with Finnish-type congenital nephrosis and nephrin-knockout mice had only narrow filtration slits that lacked the slit diaphragm network and the 35-nm-long strands but contained shorter molecular structures. The results suggest the direct involvement of nephrin molecules in constituting the macromolecule-retaining slit diaphragm and its pores.
Jorma Wartiovaara, Lars-Göran Öfverstedt, Jamshid Khoshnoodi, Jingjing Zhang, Eetu Mäkelä, Sara Sandin, Vesa Ruotsalainen, R. Holland Cheng, Hannu Jalanko, Ulf Skoglund, Karl Tryggvason
Original citation: J. Clin. Invest.114:1475–1483 (2004). doi:10.1172/JCI22562
Citation for this erratum: J. Clin. Invest.114:1820 (2004). doi:10.1172/JCI22562C1
The authors previously declared that no conflict of interest existed. The authors now wish to declare that Ulf Skoglund is the founder of Sidec Technologies AB, Sweden, which holds the patent rights for COMET, one of the software programs used in the study. COMET image processing is available for academic research through Skoglund and for commercial use through Sidec Technologies AB. The authors apologize for the oversight.