Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells
Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells
复制标题
DOI：
10.1074/jbc.m306536200
复制
发表时间：
2003-09-19
影响因子：
4.8
通讯作者：
Caplan, MJ
中科院分区：
文献类型：
--
作者：
Grimm, DH;Cai, YQ;Caplan, MJ
PKD1 和 PKD2（分别编码多囊蛋白-1 和多囊蛋白-2 的基因）的突变几乎导致了所有常染色体显性多囊肾病病例。尽管多囊蛋白被认为在体内相互作用，但这两种蛋白质在发育过程中通常表现出不同的表达模式和梯度。为了理解这种明显的差异，我们研究了多囊蛋白 2 表达的变化如何影响多囊蛋白 1 的亚细胞定位。我们发现，当多囊蛋白-1 在 PKD2 无效细胞系中单独表达时，它定位于细胞表面以及内质网。然而，当与多囊蛋白-2 共表达时，多囊蛋白-1 不会出现在细胞表面，而是与多囊蛋白-2 在内质网中完全共定位。多囊蛋白-1 融合蛋白的定位同样受到其表达水平相对于多囊蛋白-2 的变化的影响。在群体以及单个 COS-7 细胞中都观察到了这种现象。我们的数据表明多囊蛋白-1 的定位可以通过哺乳动物细胞中多囊蛋白-2 的相对表达水平进行调节。这种机制可能有助于解释多囊蛋白观察到的不同模式和表达水平，并可能为这两种蛋白质的功能在发育过程中如何调节提供线索。
Mutations in PKD1 and PKD2, the genes that encode polycystin-1 and polycystin-2 respectively, account for almost all cases of autosomal dominant polycystic kidney disease. Although the polycystins are believed to interact in vivo, the two proteins often display dissimilar patterns and gradients of expression during development. In an effort to understand this apparent discrepancy, we investigated how changes in polycystin-2 expression can affect the subcellular localization of polycystin-1. We show that, when polycystin-1 is expressed alone in a PKD2 null cell line, it localizes to the cell surface, as well as to the endoplasmic reticulum. When co-expressed with polycystin-2, however, polycystin-1 is not seen at the cell surface and co-localizes completely with polycystin-2 in the endoplasmic reticulum. The localization of a polycystin-1 fusion protein was similarly affected by changes in its level of expression relative to that of polycystin-2. This phenomenon was observed in populations as well as in individual COS-7 cells. Our data suggest that the localization of polycystin-1 can be regulated via the relative expression level of polycystin-2 in mammalian cells. This mechanism may help to explain the divergent patterns and levels of expression observed for the polycystins, and may provide clues as to how the function of these two proteins are regulated during development.