Login
Login

Nephrin

{{Short description|Mammalian protein found in Homo sapiens}}

{{Infobox_gene}}

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.{{cite web | title = Entrez Gene: NPHS1 nephrosis 1, congenital, Finnish type (nephrin)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4868}} 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,{{cite journal|vauthors=Patrakka J, Tryggvason K|title=Nephrin – a unique structural and signaling protein of the kidney filter|journal=Trends in Molecular Medicine|year=2007|volume=13|issue=9|pages=396-403|doi=10.1016/j.molmed.2007.06.006|pmid=17766183}}{{cite journal|vauthors=Martin CE, Jones N|title=Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond|journal=Frontiers in Endocrinology|year=2018|volume=9|id=Art. No. 302|doi=10.3389/fendo.2018.00302|doi-access=free|pmid=29922234|pmc=5996060}} however, the relative contribution of the slit diaphragm to exclusion of protein by the glomerulus is debated.{{cite journal|vauthors=Menzel S, Moeller MJ|title=Role of the podocyte in proteinuria|volume=26|pages=1775-1780|year=2011|journal=Pediatric Nephrology|doi=10.1007/s00467-010-1725-5|doi-access=free|pmid=21184239|pmc=3163769}} The extracellular interactions, both homophilic and heterophilic—between nephrin and NEPH1—are not completely understood. 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. Tyrosine phosphorylation at different sites on the intracellular tail contribute to the regulation of slit diaphragm formation during development and repair in pathology affecting podocytes. 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.

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.{{cite journal | vauthors = Wagner N, Morrison H, Pagnotta S, Michiels JF, Schwab Y, Tryggvason K, Schedl A, Wagner KD | title = The podocyte protein nephrin is required for cardiac vessel formation. | journal = Human Molecular Genetics | volume = 20 | issue = 11 | pages = 2182–94 | date = 2011-03-29 | pmid = 21402589 | doi = 10.1093/hmg/ddr106 | doi-access = free }}

Interactions

Nephrin has been shown to interact with:

  • CASK,
  • CD2AP,{{cite journal | vauthors = Lehtonen S, Lehtonen E, Kudlicka K, Holthöfer H, Farquhar MG | title = Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin | journal = Am. J. Pathol. | volume = 165 | issue = 3 | pages = 923–36 | date = Sep 2004 | pmid = 15331416 | pmc = 1618613 | doi = 10.1016/S0002-9440(10)63354-8 }}
  • CDH3 and
  • CTNND1,
  • FYN,{{cite journal | vauthors = Lahdenperä J, Kilpeläinen P, Liu XL, Pikkarainen T, Reponen P, Ruotsalainen V, Tryggvason K | title = Clustering-induced tyrosine phosphorylation of nephrin by Src family kinases | journal = Kidney Int. | volume = 64 | issue = 2 | pages = 404–13 | date = Aug 2003 | pmid = 12846735 | doi = 10.1046/j.1523-1755.2003.00097.x | doi-access = free }}{{cite journal | vauthors = Verma R, Wharram B, Kovari I, Kunkel R, Nihalani D, Wary KK, Wiggins RC, Killen P, Holzman LB | title = Fyn binds to and phosphorylates the kidney slit diaphragm component Nephrin | journal = J. Biol. Chem. | volume = 278 | issue = 23 | pages = 20716–23 | date = Jun 2003 | pmid = 12668668 | doi = 10.1074/jbc.M301689200 | doi-access = free }}
  • KIRREL,{{cite journal | vauthors = Liu G, Kaw B, Kurfis J, Rahmanuddin S, Kanwar YS, Chugh SS | title = Neph1 and nephrin interaction in the slit diaphragm is an important determinant of glomerular permeability | journal = J. Clin. Invest. | volume = 112 | issue = 2 | pages = 209–21 | date = Jul 2003 | pmid = 12865409 | pmc = 164293 | doi = 10.1172/JCI18242 }}{{cite journal | vauthors = Gerke P, Huber TB, Sellin L, Benzing T, Walz G | title = Homodimerization and heterodimerization of the glomerular podocyte proteins nephrin and NEPH1 | journal = J. Am. Soc. Nephrol. | volume = 14 | issue = 4 | pages = 918–26 | date = Apr 2003 | pmid = 12660326 | doi = 10.1097/01.ASN.0000057853.05686.89 | doi-access = free }} and
  • NPHS2.{{cite journal | vauthors = Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P | title = Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin | journal = J. Clin. Invest. | volume = 108 | issue = 11 | pages = 1621–9 | date = Dec 2001 | pmid = 11733557 | pmc = 200981 | doi = 10.1172/JCI12849 }}

See also

{{Clear}}

References

{{reflist|35em}}

Further reading

{{refbegin|35em}}

  • {{cite journal | vauthors = Tryggvason K | title = Nephrin: role in normal kidney and in disease. | journal = Adv. Nephrol. Necker Hosp. | volume = 31 | pages = 221–34 | year = 2002 | pmid = 11692461 }}
  • {{cite journal | vauthors = Kestilä M, Lenkkeri U, Männikkö M, Lamerdin J, McCready P, Putaala H, Ruotsalainen V, Morita T, Nissinen M, Herva R, Kashtan CE, Peltonen L, Holmberg C, Olsen A, Tryggvason K | title = Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome. | journal = Mol. Cell | volume = 1 | issue = 4 | pages = 575–82 | year = 1998 | pmid = 9660941 | doi = 10.1016/S1097-2765(00)80057-X | doi-access = free }}
  • {{cite journal | vauthors = Lenkkeri U, Männikkö M, McCready P, Lamerdin J, Gribouval O, Niaudet PM, Antignac CK, Kashtan CE, Homberg C, Olsen A, Kestilä M, Tryggvason K | title = Structure of the gene for congenital nephrotic syndrome of the finnish type (NPHS1) and characterization of mutations. | journal = Am. J. Hum. Genet. | volume = 64 | issue = 1 | pages = 51–61 | year = 1999 | pmid = 9915943 | pmc = 1377702 | doi = 10.1086/302182 }}
  • {{cite journal | vauthors = Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K | title = Nephrin is specifically located at the slit diaphragm of glomerular podocytes. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 96 | issue = 14 | pages = 7962–7 | year = 1999 | pmid = 10393930 | pmc = 22170 | doi = 10.1073/pnas.96.14.7962 | bibcode = 1999PNAS...96.7962R | doi-access = free }}
  • {{cite journal | vauthors = Bolk S, Puffenberger EG, Hudson J, Morton DH, Chakravarti A | title = Elevated frequency and allelic heterogeneity of congenital nephrotic syndrome, Finnish type, in the old order Mennonites. | journal = Am. J. Hum. Genet. | volume = 65 | issue = 6 | pages = 1785–90 | year = 2000 | pmid = 10577936 | pmc = 1288392 | doi = 10.1086/302687 }}
  • {{cite journal | vauthors = Aya K, Tanaka H, Seino Y | title = Novel mutation in the nephrin gene of a Japanese patient with congenital nephrotic syndrome of the Finnish type. | journal = Kidney Int. | volume = 57 | issue = 2 | pages = 401–4 | year = 2000 | pmid = 10652016 | doi = 10.1046/j.1523-1755.2000.00859.x | doi-access = free }}
  • {{cite journal | vauthors = Li C, Ruotsalainen V, Tryggvason K, Shaw AS, Miner JH | title = CD2AP is expressed with nephrin in developing podocytes and is found widely in mature kidney and elsewhere. | journal = Am. J. Physiol. Renal Physiol. | volume = 279 | issue = 4 | pages = F785–92 | year = 2000 | pmid = 10997929 | doi = 10.1152/ajprenal.2000.279.4.F785| s2cid = 37166239 | doi-access = free }}
  • {{cite journal | vauthors = Huber TB, Kottgen M, Schilling B, Walz G, Benzing T | title = Interaction with podocin facilitates nephrin signaling. | journal = J. Biol. Chem. | volume = 276 | issue = 45 | pages = 41543–6 | year = 2001 | pmid = 11562357 | doi = 10.1074/jbc.C100452200 | doi-access = free }}
  • {{cite journal | vauthors = Palmén T, Ahola H, Palgi J, Aaltonen P, Luimula P, Wang S, Jaakkola I, Knip M, Otonkoski T, Holthöfer H | title = Nephrin is expressed in the pancreatic beta cells. | journal = Diabetologia | volume = 44 | issue = 10 | pages = 1274–80 | year = 2002 | pmid = 11692176 | doi = 10.1007/s001250100641 | doi-access = free }}
  • {{cite journal | vauthors = Schwarz K, Simons M, Reiser J, Saleem MA, Faul C, Kriz W, Shaw AS, Holzman LB, Mundel P | title = Podocin, a raft-associated component of the glomerular slit diaphragm, interacts with CD2AP and nephrin. | journal = J. Clin. Invest. | volume = 108 | issue = 11 | pages = 1621–9 | year = 2002 | pmid = 11733557 | pmc = 200981 | doi = 10.1172/JCI12849 }}
  • {{cite journal | vauthors = Koziell A, Grech V, Hussain S, Lee G, Lenkkeri U, Tryggvason K, Scambler P | title = Genotype/phenotype correlations of NPHS1 and NPHS2 mutations in nephrotic syndrome advocate a functional inter-relationship in glomerular filtration. | journal = Hum. Mol. Genet. | volume = 11 | issue = 4 | pages = 379–88 | year = 2002 | pmid = 11854170 | doi = 10.1093/hmg/11.4.379 | doi-access = free }}
  • {{cite journal | vauthors = Yan K, Khoshnoodi J, Ruotsalainen V, Tryggvason K | title = N-linked glycosylation is critical for the plasma membrane localization of nephrin. | journal = J. Am. Soc. Nephrol. | volume = 13 | issue = 5 | pages = 1385–9 | year = 2002 | pmid = 11961028 | doi = 10.1097/01.ASN.0000013297.11876.5B | doi-access = free }}
  • {{cite journal | vauthors = Shimizu J, Tanaka H, Aya K, Ito S, Sado Y, Seino Y | title = A missense mutation in the nephrin gene impairs membrane targeting. | journal = Am. J. Kidney Dis. | volume = 40 | issue = 4 | pages = 697–703 | year = 2002 | pmid = 12324903 | doi = 10.1053/ajkd.2002.35676 }}
  • {{cite journal | vauthors = Saleem MA, Ni L, Witherden I, Tryggvason K, Ruotsalainen V, Mundel P, Mathieson PW | title = Co-localization of nephrin, podocin, and the actin cytoskeleton: evidence for a role in podocyte foot process formation. | journal = Am. J. Pathol. | volume = 161 | issue = 4 | pages = 1459–66 | year = 2002 | pmid = 12368218 | pmc = 1867300 | doi = 10.1016/S0002-9440(10)64421-5 }}
  • {{cite journal | vauthors = Kim BK, Hong HK, Kim JH, Lee HS | title = Differential expression of nephrin in acquired human proteinuric diseases. | journal = Am. J. Kidney Dis. | volume = 40 | issue = 5 | pages = 964–73 | year = 2002 | pmid = 12407641 | doi = 10.1053/ajkd.2002.36328 }}
  • {{cite journal | vauthors = Langham RG, Kelly DJ, Cox AJ, Thomson NM, Holthöfer H, Zaoui P, Pinel N, Cordonnier DJ, Gilbert RE | title = Proteinuria and the expression of the podocyte slit diaphragm protein, nephrin, in diabetic nephropathy: effects of angiotensin converting enzyme inhibition. | journal = Diabetologia | volume = 45 | issue = 11 | pages = 1572–6 | year = 2003 | pmid = 12436341 | doi = 10.1007/s00125-002-0946-y | doi-access = free }}
  • {{cite journal | vauthors = Gigante M, Monno F, Roberto R, Laforgia N, Assael MB, Livolti S, Caringella A, La Manna A, Masella L, Iolascon A | title = Congenital nephrotic syndrome of the Finnish type in Italy: a molecular approach. | journal = J. Nephrol. | volume = 15 | issue = 6 | pages = 696–702 | year = 2003 | pmid = 12495287 }}
  • {{cite journal | vauthors = Pettersson-Fernholm K, Forsblom C, Perola M, Groop PH | title = Polymorphisms in the nephrin gene and diabetic nephropathy in type 1 diabetic patients. | journal = Kidney Int. | volume = 63 | issue = 4 | pages = 1205–10 | year = 2003 | pmid = 12631336 | doi = 10.1046/j.1523-1755.2003.00855.x | doi-access = free }}
  • {{cite journal | vauthors = Kapodistria K, Tsilibary EP, Politis P, Moustardas P, Charonis A, Kitsiou P | title = Nephrin, a transmembrane protein, is involved in pancreatic beta-cell survival signaling. | journal = Mol. Cell. Endocrinol. | volume = 400 | pages = 112–28 | year = 2015 | pmid = 25448064 | doi = 10.1016/j.mce.2014.11.003 | doi-access = free }}

{{refend}}

External links

  • {{MeshName|nephrin}}

Category:Proteins