description
Nephrin 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. Nephrin is composed of an extracellular domain with eight distal IgG like domains and one proximal fibronectin type III domain, a transmembrane domain and a short intracellular domain. Nephrin molecules show both homophilic and heterophilic interactions. Among heterophilic interaction partners slit diaphragm proteins such as NEPH1, NEPH2 and NEPH3 were shown to stabilize the slit diaphragm structure. Intracellularly Podocin, CD2 associated protein (CD2AP) and adherins junction associated proteins like IQGAP, MAGI, CASK and spectrins were all shown to interact with nephrin. Hence nephrin 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. Nephrin does not only fulfill static properties within the slit diaphragm but by tyrosine phosphorylation of its cytoplasmic tail by the Src kinase Fyn it initiates the PI3K AKT signaling cascade which seems to promote antiapoptotic signals

external resources
NCBI:1270243
REACTOME:R-HSA-373753
PUBMED:12832477
PUBMED:15821412
PUBMED:16571882
PUBMED:17766183
PUBMED:10541305
PUBMED:19649571
PUBMED:10393930
PUBMED:15994232

genes
ACTN4 , ACTN1 , ACTN2 , ACTN3 , FYN , NCK1 , NPHS1 , PIK3CA , PIK3CB , PIK3R1 , PIK3R2 , SPTAN1 , SPTBN1 , NCK2 , CASK , IQGAP1 , WASL , MAGI2 , CD2AP , KIRREL1 , KIRREL2 , KIRREL3 ,