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Nephrin is a protein necessary for the proper functioning of the renal filtration barrier. The renal filtration barrier consists of fenestrated endothelial cells, the glomerular basement membrane, and the podocytes of epithelial cells. Nephrin is a transmembrane protein that is a structural component of the slit diaphragm.[5] It is present on the tips of the podocytes as an intricate mesh connecting adjacent foot 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 and NEPH1—are not completely understood.[6] In addition to eight immunoglobulin G–like motifs and a fibronectin 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 onto lipid 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 with congenital nephrotic syndrome of the Finnish type and causes massive amounts of protein to be leaked into the urine, or proteinuria. Nephrin is also required for cardiovascular development.[9]
Nephrin was first identified in 1998 by Karl Tryggvason and colleagues, who discovered mutations in the NPHS1 gene in a Finnish newborn with congenital nephrotic syndrome of the Finnish type.[16][17] Based on its structural features, the authors concluded that nephrin was likely to function as both an adhesion receptor and a signalling protein.[18]
12345Patrakka 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.
↑Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, etal. (March 1998). "Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome". Molecular Cell. 1 (4): 575–582. doi:10.1016/S1097-2765(00)80057-X. PMID9660941.
↑Shih NY, Li J, Karpitskii V, Nguyen A, Dustin ML, Kanagawa O, etal. (October 1999). "Congenital nephrotic syndrome in mice lacking CD2-associated protein". Science. 286 (5438). New York, N.Y.: 312–315. doi:10.1126/science.286.5438.312. PMID10514378.
↑Li M, Armelloni S, Edefonti A, Messa P, Rastaldi MP (April 2013). "Fifteen years of research on nephrin: what we still need to know". Nephrology, Dialysis, Transplantation. 28 (4): 767–770. doi:10.1093/ndt/gfs522. hdl:2434/590872. PMID23139403.
Shimizu J, Tanaka H, Aya K, Ito S, Sado Y, Seino Y (2002). "A missense mutation in the nephrin gene impairs membrane targeting". American Journal of Kidney Diseases. 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". American Journal of Kidney Diseases. 40 (5): 964–973. doi:10.1053/ajkd.2002.36328. PMID12407641.
Gigante M, Monno F, Roberto R, Laforgia N, Assael MB, Livolti S, etal. (2003). "Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach". Journal of Nephrology. 15 (6): 696–702. PMID12495287.
