Renal Section, Department of Medicine, Boston University Medical Center, Boston, MA 02118, USA.
Cell Rep. 2012 Jul 26;2(1):52-61. doi: 10.1016/j.celrep.2012.06.002. Epub 2012 Jul 12.
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.
Robo2 是排斥性导向线索 Slit 的细胞表面受体，参与轴突导向和神经元迁移。 Nephrin 是一种足细胞裂孔隔膜蛋白，在肾脏肾小球滤过屏障中发挥作用。在这里，我们报告 Robo2 在小鼠足细胞的基底表面表达，并与 Nephrin 共定位。生化研究表明，Robo2 通过衔接蛋白 Nck 在肾脏中与 Nephrin 形成复合物。与促进肌动蛋白聚合的 Nephrin 作用相反，Slit2-Robo2 信号抑制 Nephrin 诱导的肌动蛋白聚合。此外，在发生足细胞突起结构改变的 Robo2 敲除小鼠中，与 Nephrin 相关的 F-肌动蛋白的量增加。遗传相互作用研究进一步表明，Robo2 的缺失减轻了 Nephrin 缺失小鼠中异常的足细胞结构表型。这些结果表明 Robo2 信号作为 Nephrin 的负调节剂影响足细胞突起结构。
