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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton
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The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein associated with the actin cytoskeleton

机译：多囊肾疾病蛋白PKD2与与肌动蛋白细胞骨架相关的蛋白Hax-1相互作用

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摘要

Despite the recent positional cloning of the PKD1 and PKD2 genes, which are mutated in the great majority of patients with autoso- mal-dominant polycystic kidney disease (PKD), the pathogenic mechanism for cyst formation is still unclear. The finding, that the IKD1 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 experi- ments 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 cortattin, 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 wild- type PKD2 protein. thus leading to cystic enlargement of tubular Structures in the kidney. liver, and pancreas.
机译：尽管最近在大多数常染色体显性多囊性肾病（PKD）患者中突变了PKD1和PKD2基因的位置克隆，但囊肿形成的致病机制仍不清楚。 IKD1和PKD2蛋白通过其COOH末端彼此相互作用的发现。提示这两种蛋白是同一蛋白复合物或信号转导途径的一部分。使用带有PKD2蛋白的酵母双杂交筛选，我们分离了PKD2相互作用蛋白Hax-1。通过与PKD2紧密相关的蛋白质PKD2L无法与Hax-1相互作用这一事实证明了相互作用的特异性。免疫荧光实验表明，在大多数细胞中PKD2和Hax-1共定位在细胞体内，但在某些细胞中PKD2和Hax-1也被分为细胞过程和片状脂膜。此外，我们证明了Hax-1与F-肌动蛋白结合蛋白cortattin之间存在关联，这表明PKD2与肌动蛋白细胞骨架之间存在联系。我们推测PKD2参与了细胞-基质接触的形成，而没有野生型PKD2蛋白则功能障碍。因此导致肾小管结构的囊性扩大。肝脏和胰腺。

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