Reactome | Nephrin family interactions

Nephrin family interactions

Stable Identifier

R-HSA-373753

DOI

10.3180/REACT_23832.1

Type

Pathway

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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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 in between 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
12832477	Nephrin and CD2AP associate with phosphoinositide 3-OH kinase and stimulate AKT-dependent signaling Walz, G, Schermer, B, Kim, J, Borner, C, Keil, A, Egger, L, Lecha, RL, Schmidts, M, Huber, TB, Shaw, AS, Hartleben, B, Benzing, T, Pavenstädt, H	Mol Cell Biol	2003
15821412	The slit diaphragm: a signaling platform to regulate podocyte function Benzing, T, Huber, TB	Curr Opin Nephrol Hypertens	2005
16571882	Hereditary proteinuria syndromes and mechanisms of proteinuria Wartiovaara, J, Patrakka, J, Tryggvason, K	N Engl J Med	2006
10393930	Nephrin is specifically located at the slit diaphragm of glomerular podocytes Holmberg, C, Wartiovaara, J, Ljungberg, P, Lenkkeri, U, Jalanko, H, Tryggvason, K, Kestilä, M, Ruotsalainen, V	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 Kudlicka, K, Zhou, H, Lehtonen, S, Farquhar, MG, Iino, N, Ryan, JJ	Proc Natl Acad Sci U S A	2005
17766183	Nephrin--a unique structural and signaling protein of the kidney filter Tryggvason, K, Patrakka, J	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 Antignac, C, Zenker, M, Machuca, E	J Mol Med	2009