Nephrin family interactions

Stable Identifier
R-HSA-373753
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Pathway
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Homo sapiens
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Nephrin (NPHS1) is a member of the Super-IgG-Molecule family and is most prominently expressed in kidney podocytes. It is a major if not the most important structural component of the slit diaphragm, a modified adherens junction inbetween these cells. NPHS1 has an extracellular domain that contains eight distal IgG like domains and one proximal fibronectin type III domain, a transmembrane domain and a short intracellular domain. NPHS1 molecules show both homophilic and heterophilic interactions. Among heterophilic interaction partners, slit diaphragm proteins such as Kin of IRRE-like protein 1 (KIRREL, Nephrin-like protein 1, NEPH1), KIRREL3 (NEPH2) and KIRREL2 (NEPH3) were shown to stabilize the slit diaphragm structure. Intracellularly Podocin (NPHS2), CD2 associated protein (CD2AP) and adherins junction associated proteins like IQGAP, MAGI, CASK and spectrins all interact with NPHS1. Hence it seems to play a major role in organizing the molecular structure of the slit diaphragm itself and via its binding partners links it to the actin cytoskeleton. NPHS1 tyrosine phosphorylation by the Src kinase FYN initiates the PI3K-AKT signaling cascade, which seems to promote antiapoptotic signals.

Literature References
PubMed ID Title Journal Year
15821412 The slit diaphragm: a signaling platform to regulate podocyte function

Huber, TB, Benzing, T

Curr Opin Nephrol Hypertens 2005
12832477 Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling

Huber, TB, Hartleben, B, Kim, J, Schmidts, M, Schermer, B, Keil, A, Egger, L, Lecha, RL, Borner, C, Pavenstädt, H, Shaw, AS, Walz, G, Benzing, T

Mol Cell Biol 2003
16571882 Hereditary proteinuria syndromes and mechanisms of proteinuria

Tryggvason, K, Patrakka, J, Wartiovaara, J

N Engl J Med 2006
10393930 Nephrin is specifically located at the slit diaphragm of glomerular podocytes

Ruotsalainen, V, Ljungberg, P, Wartiovaara, J, Lenkkeri, U, Kestilä, M, Jalanko, H, Holmberg, C, Tryggvason, K

Proc Natl Acad Sci U S A 1999
15994232 Cell junction-associated proteins IQGAP1, MAGI-2, CASK, spectrins, and alpha-actinin are components of the nephrin multiprotein complex

Lehtonen, S, Ryan, JJ, Kudlicka, K, Iino, N, Zhou, H, Farquhar, MG

Proc Natl Acad Sci U S A 2005
17766183 Nephrin--a unique structural and signaling protein of the kidney filter

Patrakka, J, Tryggvason, K

Trends Mol Med 2007
10541305 Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm

Tryggvason, K

J Am Soc Nephrol 1999
19649571 Genetics of nephrotic syndrome: new insights into molecules acting at the glomerular filtration barrier

Zenker, M, Machuca, E, Antignac, C

J Mol Med 2009
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