Heterodimerization of nephrin and NEPH2/NEPH3 Cis-Heterodimerization of nephrin and NEPH1 Nephrin binds NCK Phosphorylation of nephrin by the Src family kinase Fyn Nephrin trans-homophilic interaction Nephrin interacts with Podocin Nephrin mediated activation of N-WASP Nephrin binds CD2AP Interaction of nephrin with adherens junction-associated proteins Interaction of IQGAP1 with nephrin Nephrin binds CASK p85 associates with both p-Nephrin and CD2AP PathwayStep4841 PathwayStep4842 PathwayStep4843 PathwayStep4844 PathwayStep4840 PathwayStep4836 PathwayStep4837 PathwayStep4834 PathwayStep4835 PathwayStep4833 PathwayStep4838 PathwayStep4839 Nephrin interactions Authored: de Bono, B, Garapati, P V, 2008-02-26 12:30:30 Edited: Garapati, P V, 2010-03-01 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. Pubmed10393930 Pubmed10541305 Pubmed12832477 Pubmed15821412 Pubmed15994232 Pubmed16571882 Pubmed17766183 Pubmed19649571 Reactome Database ID Release 43373753 Reactome, http://www.reactome.org ReactomeREACT_23832 Reviewed: Huber, TB, Grahammer, Florian, 2010--0-5-