Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif
Polycystin-2 traffics to cilia independently of polycystin-1 by using an N-terminal RVxP motif
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DOI：
10.1242/jcs.02818
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发表时间：
2006-04-01
影响因子：
4
通讯作者：
Somlo, S
中科院分区：
文献类型：
--
作者：
Geng, L;Okuhara, D;Somlo, S
原发性纤毛在常染色体显性遗传性多囊肾病（ADPKD）的发病机制中起关键作用。受影响的蛋白质，多囊蛋白-1（PC 1）和多囊蛋白-2（PC 2），相互作用，并在纤毛中表达。我们发现，COOH末端截短的PC 2（PC 2-L703 X），缺乏PC 1相互作用区域，仍然交通纤毛。我们研究了PC 2在几个组织和细胞缺乏PC 1的表达，发现PC 2在纤毛中独立于PC 1表达。我们使用N-末端缺失构建体将纤毛运输所需的结构域缩小到PC 2的前15个氨基酸，并鉴定了纤毛定位所需的保守基序R（6）RNP。N-末端15个氨基酸也足以定位纤毛中的异源蛋白。PC 2具有内源性纤毛运输信息，存在于PKD 1突变引起的囊肿内衬细胞的纤毛中。
Primary cilia play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The affected proteins, polycystin-1 (PC1) and polycystin-2 (PC2), interact with each other and are expressed in cilia. We found that COOH-terminal truncated PC2 (PC2-L703X), lacking the PC1 interaction region, still traffics to cilia. We examined PC2 expression in several tissues and cells lacking PC1 and found that PC2 is expressed in cilia independently of PC1. We used N-terminal deletion constructs to narrow the domain necessary for cilia trafficking to the first 15 amino acids of PC2 and identified a conserved motif, R(6)VxP, that is required for cilial localization. The N-terminal 15 amino acids are also sufficient to localize heterologous proteins in cilia. PC2 has endogenous cilia trafficking information and is present in cilia of cells lining cysts that result from mutations in PKD1.