MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin
MAGI-1 is a component of the glomerular slit diaphragm that is tightly associated with nephrin
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DOI：
10.1038/labinvest.3700347
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发表时间：
2005-12-01
影响因子：
5
通讯作者：
Hata, Y
中科院分区：
文献类型：
--
作者：
Hirabayashi, S;Mori, H;Hata, Y
MAGI-1是一种膜相关蛋白，具有一个鸟苷酸激酶、六个PSD-95/Dlg-A/ZO-1（PDZ）和两个WW结构域，定位于上皮细胞的紧密连接处。MAGI-1与各种蛋白质相互作用，并被认为是一种支架蛋白。在前期的研究中，我们发现了一种与MAGI-1相互作用的细胞粘附分子Junctional adhesion molecule 4（JAM 4）。这两种蛋白质在肾脏的肾小球足细胞中高度表达，并且部分共定位。本研究通过酵母双杂交筛选，进一步寻找MAGI-1在肾脏中的结合伴侣，获得nephrin。Nephrin是一种细胞粘附分子，特异性地定位于足细胞的相邻足突之间的狭缝隔膜。生物化学研究表明，nephrin通过其羧基末端直接结合MAGI-1的中间PDZ结构域，但不结合ZO-1。MAGI-1在体外与nephrin和JAM 4形成三重复合物。免疫电子显微镜显示MAGI-1的定位仅限于狭缝隔膜，而JAM 4也分布在足细胞的顶膜上。在嘌呤霉素氨基胍诱导的肾病足细胞中，MAGI-1与nephrin定位在移位的狭缝隔膜处。这些数据表明MAGI-1是狭缝隔膜的组分，并且在体内与nephrin和JAM 4紧密相互作用。MAGI-1可能在裂隙隔水平上决定顶侧区和侧侧区之间的边界。
MAGUK with inverted domain structure-1 (MAGI-1) is a membrane-associated protein with one guanylate kinase, six PSD-95/Dlg-A/ZO-1 (PDZ), and two WW domains and is localized at tight junctions in epithelial cells. MAGI-1 interacts with various proteins and is proposed to function as a scaffold protein. In the previous study, we discovered a MAGI-1-interacting cell adhesion molecule junctional adhesion molecule 4 (JAM4). Both proteins are highly expressed in glomerular podocytes in the kidney and partially colocalized. In this study, we have further searched for a binding partner of MAGI-1 in the kidney through yeast two-hybrid screening and obtained nephrin. Nephrin is a cell adhesion molecule specifically localized at the slit diaphragm between neighboring foot processes of podocytes. Biochemical studies reveal that nephrin directly binds to the middle PDZ domains of MAGI-1 through its carboxyl terminus but does not bind to ZO-1. MAGI-1 forms a tripartite complex with nephrin and JAM4 in vitro. Immunoelectron microscopy shows that the localization of MAGI-1 is restricted to the slit diaphragm, whereas JAM4 is also distributed on apical membranes of podocytes. In puromycin aminonucleoside-induced nephrotic podocytes, MAGI-1 is localized with nephrin at the displaced slit diaphragm. These data indicate that MAGI-1 is a component of the slit diaphragm and tightly interacts with nephrin and JAM4 in vivo. MAGI-1 may play a role in determining the boundary between the apical and the bosolateral domain at the level of slit diaphragm.