Geng Lin, Okuhara Dayne, Yu Zhiheng, Tian Xin, Cai Yiqiang, Shibazaki Sekiya, Somlo Stefan
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
J Cell Sci. 2006 Apr 1;119(Pt 7):1383-95. doi: 10.1242/jcs.02818. Epub 2006 Mar 14.
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, R6VxP, 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.
原发性纤毛在常染色体显性多囊肾病（ADPKD）的发病机制中起关键作用。受影响的蛋白质多囊蛋白-1（PC1）和多囊蛋白-2（PC2）相互作用并在纤毛中表达。我们发现，缺少PC1相互作用区域的COOH末端截短型PC2（PC2-L703X）仍能转运至纤毛。我们检测了PC2在几种缺乏PC1的组织和细胞中的表达，发现PC2在纤毛中的表达独立于PC1。我们使用N末端缺失构建体将纤毛转运所需结构域缩小至PC2的前15个氨基酸，并鉴定出一个保守基序R6VxP，这是纤毛定位所必需的。N末端的15个氨基酸也足以将异源蛋白定位于纤毛中。PC2具有内源性纤毛转运信息，并且存在于由PKD1突变导致的囊肿内衬细胞的纤毛中。
