KIBRA modulates directional migration of podocytes
KIBRA modulates directional migration of podocytes
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DOI：
10.1681/asn.2007080916
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发表时间：
2008-10-01
影响因子：
13.6
通讯作者：
Pavenstaedt, Hermann
中科院分区：
文献类型：
--
作者：
Duning, Kerstin;Schurek, Eva-Maria;Pavenstaedt, Hermann
大分子的不对称递送和分布对于细胞极性和分化、分裂和信号传导等细胞功能至关重要。足细胞（极化上皮细胞）的损伤会改变肌动蛋白网的动力学，导致足突回缩和蛋白尿。尽管特定蛋白质-蛋白质相互作用的时空控制对于细胞极性的建立至关重要，但控制极性依赖性分化和分裂的机制尚不完全清楚。在本研究中，使用足细胞 cDNA 文库和极性蛋白 PATJ 作为诱饵进行酵母双杂交筛选。蛋白质 KIBRA 被鉴定为 PATJ 的相互作用伴侣，定位于足细胞、管状结构和集合管。 KIBRA 的最后四个氨基酸介导与 PATJ 的第八个 PDZ 结构域的结合。此外，KIBRA 直接与突触足蛋白（足细胞细胞骨架的重要组织者）结合。永生化足细胞中 KIBRA 的稳定敲低会损害定向细胞迁移，表明 KIBRA 通过连接极性蛋白和细胞骨架相关蛋白复合物来调节足细胞的运动性。
Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein-protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.