Nephrin is aprotein necessary for the proper functioning of therenal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and thepodocytes of epithelial cells. Nephrin is atransmembrane protein that is a structural component of theslit diaphragm.[5] It is present on the tips of the podocytes as an intricate mesh connecting adjacentfoot processes. Nephrin contributes to the strong size selectivity of the slit diaphragm,[6][7] however, the relative contribution of the slit diaphragm to exclusion of protein by the glomerulus is debated.[6][8] The extracellular interactions, both homophilic and heterophilic—between nephrin andNEPH1—are not completely understood.[6] In addition to eightimmunoglobulin G–like motifs and afibronectin type 3 repeat, nephrin has a single transmembrane domain and a short intracellular tail.[6][7] Tyrosine phosphorylation at different sites on the intracellular tail contribute to the regulation of slit diaphragm formation during development[7] and repair in pathology affecting podocytes.[6][7]Podocin may interact with nephrin to guide it ontolipid rafts in podocytes, requiring the integrity of an arginine residue of nephrin at position 1160.[7]
A defect in the gene for nephrin,NPHS1, is associated withcongenital nephrotic syndrome ofthe Finnish type and causes massive amounts of protein to be leaked into the urine, orproteinuria. Nephrin is also required for cardiovascular development.[9]
^abcdePatrakka J, Tryggvason K (2007). "Nephrin – a unique structural and signaling protein of the kidney filter".Trends in Molecular Medicine.13 (9):396–403.doi:10.1016/j.molmed.2007.06.006.PMID17766183.
Shimizu J, Tanaka H, Aya K, Ito S, Sado Y, Seino Y (2002). "A missense mutation in the nephrin gene impairs membrane targeting".Am. J. Kidney Dis.40 (4):697–703.doi:10.1053/ajkd.2002.35676.PMID12324903.
Kim BK, Hong HK, Kim JH, Lee HS (2002). "Differential expression of nephrin in acquired human proteinuric diseases".Am. J. Kidney Dis.40 (5):964–73.doi:10.1053/ajkd.2002.36328.PMID12407641.
Gigante M, Monno F, Roberto R, Laforgia N, Assael MB, Livolti S, Caringella A, La Manna A, Masella L, Iolascon A (2003). "Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach".J. Nephrol.15 (6):696–702.PMID12495287.
