The polycystic kidney disease 1 gene product modulates Wnt signaling
The polycystic kidney disease 1 gene product modulates Wnt signaling
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DOI：
10.1074/jbc.274.8.4947
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发表时间：
1999-02-19
影响因子：
4.8
通讯作者：
Walz, G
中科院分区：
文献类型：
--
作者：
Kim, E;Arnould, T;Walz, G
两个不同的信号通路，包括Wnt信号和多囊蛋白，被发现对正常的肾脏发育至关重要。肾小管的形成需要某些Wnt蛋白的存在，而多囊蛋白的突变阻碍了肾小管上皮细胞的终末分化，导致巨大的囊性肾脏的发展，这是常染色体显性多囊肾病的特征。多囊蛋白是一种完整的膜蛋白，由几个细胞外基序组成，通过多个跨膜结构域连接到一个功能活跃的细胞质结构域，这些基序代表细胞与细胞和基质之间的相互作用。我们在此报道，多囊藻毒素C末端胞质结构域的表达稳定了可溶性内源性β-连环蛋白，并刺激了人胚胎肾细胞中依赖于TCF的基因转录。显微注射多囊藻毒素C末端胞质DO主要诱导斑马鱼背化，我们的发现表明多囊藻毒素在肾脏发育过程中具有调节Wnt信号的能力。
Two distinct signaling pathways, involving Wnt signaling and polycystin, have been found to be critical for normal kidney development. Renal tubulogenesis requires the presence of certain Wnt proteins, whereas mutations in polycystin impede the terminal differentiation of renal tubular epithelial cells, causing the development of large cystic kidneys that characterize autosomal dominant polycystic kidney disease. Polycystin is an integral membrane protein, consisting of several extracellular motifs indicative of cell-cell and cell-matrix interactions, coupled through multiple transmembrane domains to a functionally active cytoplasmic domain. We report here that expression of the C-terminal cytoplasmic domain of polycystin stabilizes soluble endogenous beta-catenin and stimulates TCF-dependent gene transcription in human embryonic kidney cells. Microinjection of the polycystin C-terminal cytoplasmic do main induces dorsalization in zebrafish, Our findings suggest that polycystin has the capacity to modulate Wnt signaling during renal development.