机械刺激诱导多囊蛋白-1 C末端的裂解和核转位。
Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus.
作者信息
Chauvet Veronique, Tian Xin, Husson Herve, Grimm David H, Wang Tong, Hiesberger Thomas, Igarashi Peter, Bennett Anton M, Ibraghimov-Beskrovnaya Oxana, Somlo Stefan, Caplan Michael J
机构信息
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
出版信息
J Clin Invest. 2004 Nov;114(10):1433-43. doi: 10.1172/JCI21753.
Abstract
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 functions, 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.
摘要
多囊蛋白-1由一个在常染色体显性多囊肾病（ADPKD）中发生突变的基因编码，它参与细胞与基质的相互作用以及纤毛信号传导。然而，其发挥功能的确切机制仍不清楚。在此我们发现，多囊蛋白-1会发生蛋白水解切割，释放出其C末端尾巴（CTT），该尾巴进入细胞核并启动信号传导过程。这种切割在体内与机械刺激的改变相关联。多囊蛋白-2是ADPKD中发生突变的第二个基因的产物，它调节多囊蛋白-1 CTT的信号特性。这些数据揭示了一条多囊蛋白-1直接将信息传递至细胞核的新途径。
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