Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure.
Inhibitory effects of Robo2 on nephrin: a crosstalk between positive and negative signals regulating podocyte structure.
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DOI：
10.1016/j.celrep.2012.06.002
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发表时间：
2012-07-26
期刊：
影响因子：
8.8
通讯作者：
Lu W
中科院分区：
文献类型：
--
作者：
Fan X;Li Q;Pisarek-Horowitz A;Rasouly HM;Wang X;Bonegio RG;Wang H;McLaughlin M;Mangos S;Kalluri R;Holzman LB;Drummond IA;Brown D;Salant DJ;Lu W
Robo 2是排斥性导向因子Slit的细胞表面受体，参与轴突导向和神经元迁移。Nephrin是一种足细胞裂膜蛋白，在肾小球滤过屏障中发挥作用。在这里，我们报告说，Robo 2表达在小鼠足细胞的基底表面，并与nephrin共定位。生化研究表明，Robo 2通过接头蛋白Nck与肾脏中的nephrin形成复合物。与nephrin促进肌动蛋白聚合的作用相反，Slit 2-Robo 2信号传导抑制nephrin诱导的肌动蛋白聚合。此外，与nephrin相关的F-肌动蛋白的量在Robo 2基因敲除小鼠中增加，这些小鼠的足细胞足突结构发生改变。遗传相互作用研究进一步揭示了Robo 2的缺失导致nephrin敲除小鼠中异常足细胞结构表型。这些结果表明，Robo 2信号作为nephrin的负调节剂，影响足细胞足突结构。
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 co-localizes 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.
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影响因子：
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