The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton
The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton
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DOI：
10.1073/pnas.97.8.4017
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发表时间：
2000-04-11
影响因子：
11.1
通讯作者：
Witzgall, R
中科院分区：
文献类型：
--
作者：
Gallagher, AR;Cedzich, A;Witzgall, R
PKD1和PKD2基因在大多数常染色体显性多囊肾病（PKD）患者中发生突变，尽管最近对其进行了定位克隆，但囊肿形成的致病机制仍不清楚。发现PKD1和PKD2蛋白通过其COOH末端相互作用，表明这两种蛋白是同一蛋白复合物或信号转导途径的一部分。利用酵母与PKD2蛋白的双杂交筛选，我们分离到了PKD2与Hax-1相互作用的蛋白Hax-1，与PKD2密切相关的蛋白PKD2L无法与Hax-1相互作用，免疫荧光实验表明，在大多数细胞中，PKD2与Hax-1共定位在细胞体中，但在一些细胞中，PKD2与Hax-1也被分类为细胞突和板足。此外，我们证实了Hax-1与f -肌动蛋白结合蛋白之间的关联，这表明PKD2与肌动蛋白细胞骨架之间存在联系。我们推测PKD2参与细胞-基质接触的形成，如果没有野生型PKD2蛋白，细胞-基质接触就会功能失调，从而导致肾、肝和胰腺管状结构的囊性增大。
Despite the recent positional cloning of the PKD1 and PKD2 genes, which are mutated in the great majority of patients with autosomal-dominant polycystic kidney disease (PKD), the pathogenic mechanism for cyst formation is still unclear, The finding, that the PKD1 and PKD2 proteins interact with each other through their COOH termini, suggests that both proteins are part of the same protein complex or signal transduction pathway. Using a yeast two-hybrid screen with the PKD2 protein, we isolated the PKD2-interacting protein Hax-1, The specificity of the interaction was demonstrated by the fact that PKD2L, a protein closely related to PKD2, failed to interact with Hax-1, Immunofluorescence experiments showed that in most cells PKD2 and Hax-1 colocalized in the cell body, but in some cells PKD2 and Hax-1 also were sorted into cellular processes and lamellipodia, Furthermore we demonstrated an association between Hax-1 and the F-actin-binding protein cortactin, which suggests a link between PKD2 and the actin cytoskeleton, We speculate that PKD2 is involved in the formation of cell-matrix contacts, which are dysfunctional without a wildtype PKD2 protein, thus leading to cystic enlargement of tubular structures in the kidney, liver, and pancreas.