Interaction with podocin facilitates nephrin signaling
Interaction with podocin facilitates nephrin signaling
复制标题
DOI：
10.1074/jbc.c100452200
复制
发表时间：
2001-11-09
影响因子：
4.8
通讯作者：
Benzing, T
中科院分区：
文献类型：
--
作者：
Huber, TB;Köttgen, M;Benzing, T
编码肾小球足细胞蛋白nephrin和podocin的基因NPHS 1或NPHS 2的突变引起类固醇抵抗性蛋白尿。此外，缺乏CD 2相关蛋白（CD 2AP）的小鼠会发生类似于NPHS突变的肾病综合征，这表明所有三种蛋白质对肾小球足细胞的完整性至关重要。虽然这两种蛋白质的精确肾小球功能仍然未知，但已经表明nephrin形成拉链样相互作用以维持足细胞足突的结构。我们现在证明nephrin是一种信号分子，它刺激丝裂原活化蛋白激酶。肾蛋白诱导的信号传导被podocin大大增强，podocin结合到肾蛋白的胞质尾。突变分析表明，通过肾蛋白-podocin复合物的异常或低效信号传导有助于足细胞功能障碍和蛋白尿的发展。
Mutations of NPHS1 or NPHS2, the genes encoding for the glomerular podocyte proteins nephrin and podocin, cause steroid-resistant proteinuria. In addition, mice lacking CD2-associated protein (CD2AP) develop a nephrotic syndrome that resembles NPHS mutations suggesting that all three proteins are essential for the integrity of glomerular podocytes. Although the precise glomerular function of either protein remains unknown, it has been suggested that nephrin forms zipper-like interactions to maintain the structure of podocyte foot processes. We demonstrate now that nephrin is a signaling molecule, which stimulates mitogen-activated protein kinases. Nephrin-induced signaling is greatly enhanced by podocin, which binds to the cytoplasmic tail of nephrin. Mutational analysis suggests that abnormal or inefficient signaling through the nephrin-podocin complex contributes to the development of podocyte dysfunction and proteinuria.