| Literature DB >> 22840396 |
Xueping Fan1, Qinggang Li, Anna Pisarek-Horowitz, Hila Milo Rasouly, Xiangling Wang, Ramon G Bonegio, Hang Wang, Margaret McLaughlin, Steve Mangos, Raghu Kalluri, Lawrence B Holzman, Iain A Drummond, Dennis Brown, David J Salant, Weining Lu.
Abstract
Robo2 is the cell surface receptor for the repulsive guidance cue Slit and is involved in axon guidance and neuronal migration. Nephrin is a podocyte slit-diaphragm protein that functions in the kidney glomerular filtration barrier. Here, we report that Robo2 is expressed at the basal surface of mouse podocytes and colocalizes with nephrin. Biochemical studies indicate that Robo2 forms a complex with nephrin in the kidney through adaptor protein Nck. In contrast to the role of nephrin that promotes actin polymerization, Slit2-Robo2 signaling inhibits nephrin-induced actin polymerization. In addition, the amount of F-actin associated with nephrin is increased in Robo2 knockout mice that develop an altered podocyte foot process structure. Genetic interaction study further reveals that loss of Robo2 alleviates the abnormal podocyte structural phenotype in nephrin null mice. These results suggest that Robo2 signaling acts as a negative regulator on nephrin to influence podocyte foot process architecture.Entities:
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Year: 2012 PMID： 22840396 PMCID： PMC3627357 DOI： 10.1016/j.celrep.2012.06.002
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423