Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus
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DOI：
10.1172/jci200421753
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发表时间：
2004-11-01
影响因子：
15.9
通讯作者：
Caplan, MJ
中科院分区：
文献类型：
--
作者：
Chauvet, V;Tian, X;Caplan, MJ
多囊蛋白-1由常染色体显性遗传性多囊肾病(ADPKD)中突变的基因编码，参与细胞-基质相互作用和纤毛信号转导。然而，它发挥作用的确切机制仍不清楚。在这里，我们发现多囊蛋白-1经历了蛋白水解性切割，释放其C末端尾巴(CTT)，进入细胞核并启动信号传递过程。卵裂发生在体内，与机械刺激的变化有关。多囊蛋白-2是ADPKD中第二个基因突变的产物，它调节多囊蛋白-1 CTT的信号特性。这些数据揭示了多囊蛋白-1将信息直接传递到细胞核的一种新途径。
Polycystin-1, which is encoded by a gene that is mutated in autosomal dominant polycystic kidney disease (ADPKD), is involved in cell-matrix interactions as well as in ciliary signaling. The precise mechanisms by which it fimctions, however, remain unclear. Here we find that polycystin-1 undergoes a proteolytic cleavage that releases its C-terminal tail (CTT), which enters the nucleus and initiates signaling processes. The cleavage occurs in vivo in association with alterations in mechanical stimuli. Polycystin-2, the product of the second gene mutated in ADPKD, modulates the signaling properties of the polycystin-1 CTT. These data reveal a novel pathway by which polycystin-1 transmits messages directly to the nucleus.