The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia
The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia
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DOI：
10.1097/01.asn.0000029587.47950.25
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发表时间：
2002-10-01
影响因子：
13.6
通讯作者：
Guay-Woodford, LM
中科院分区：
文献类型：
--
作者：
Yoder, BK;Hou, XY;Guay-Woodford, LM
最近的证据表明，结构和/或功能缺陷之间的联系，在初级顶端纤毛的脊椎动物上皮细胞和多囊肾病（PKD）。在秀丽隐杆线虫中，PKD相关蛋白质的蛋白质直向同源物，多囊蛋白-1（LOV-1）、多囊蛋白-2（PKD-2）和polaris（OSM-5），共定位于雄性特异性感觉神经元的纤毛中，并且这些蛋白质的缺陷引起纤毛结构和/或功能的异常。本研究试图确定哺乳动物多囊蛋白是否在肾上皮的初级纤毛中表达，以及这些蛋白是否与polaris和cystin（一种新描述的在cpk小鼠中被破坏的纤毛相关蛋白）共定位。为了开始解决这个问题，PKD 1，PKD 2，Tg 737，和cpk基因编码的蛋白质产物的表达进行了检查，在小鼠皮质集合管（mCCD）细胞中使用一系列先前充分表征的抗体的免疫荧光为基础的方法。使mCCD细胞在细胞培养插入物上生长以优化细胞极化和纤毛形成。这些数据表明，多囊蛋白-1和多囊蛋白-2与polaris和cystin共定位在纤毛中，多囊蛋白-1和多囊蛋白-2是参与常染色体显性多囊肾病的主要蛋白质，polaris和cystin是分别在常染色体隐性多囊肾病的Tg 737（orpk）和cpk小鼠模型中被破坏的蛋白质。这些数据增加了越来越多的证据表明，初级纤毛在肾上皮细胞的正常生理功能中起着关键作用，纤毛功能的缺陷有助于PKD的发病机制。
Recent evidence has suggested an association between structural and/or functional defects in the primary apical cilium of vertebrate epithelia and polycystic kidney disease (PKD). In Caenorhabditis elegans, the protein orthologues of the PKD-related proteins, polycystin-1 (LOV-1), polycystin-2 (PKD2), and polaris (OSM-5), co-localize in the cilia of male-specific sensory neurons, and defects in these proteins cause abnormalities of cilia structure and/or function. This study sought to determine whether the mammalian polycystins are expressed in primary cilia of renal epithelia and whether these proteins co-localize with polaris and cystin, the newly described, cilia-associated protein that is disrupted in the cpk mouse. To begin to address this issue, the expression of the protein products encoded by the PKD1, PKD2, Tg737, and cpk genes were examined in mouse cortical collecting duct (mCCD) cells using an immunofluorescence-based approach with a series of previously well-characterized antibodies. The mCCD cells were grown on cell culture inserts to optimize cell polarization and cilia formation. The data demonstrate colocalization in cilia of polycystin-1 and polycystin-2, which are the principal proteins involved in autosomal dominant polycystic kidney disease, with polaris and cystin, which are proteins that are disrupted in the Tg737(orpk) and cpk mouse models of autosomal recessive polycystic kidney disease, respectively. These data add to a growing body of evidence that suggests that primary cilium plays a key role in normal physiologic functions of renal epithelia and that defects in ciliary function contribute to the pathogenesis of PKD.