多囊蛋白与钙信号在细胞死亡与存活中的作用。
Polycystin and calcium signaling in cell death and survival.
机构信息
Department of Pharmacology, Yale University, 333 Cedar St, New Haven, CT, 06520, USA.
Department of Pharmacology, Yale University, 333 Cedar St, New Haven, CT, 06520, USA; Department of Cellular and Molecular Physiology, Yale University, 333 Cedar St, New Haven, CT, 06520, USA.
出版信息
Cell Calcium. 2018 Jan;69:37-45. doi: 10.1016/j.ceca.2017.05.011. Epub 2017 May 24.
Abstract
Mutations in polycystin-1 (PC1) and polycystin-2 (PC2) result in a commonly occurring genetic disorder, called Autosomal Dominant Polycystic Kidney Disease (ADPKD), that is characterized by the formation and development of kidney cysts. Epithelial cells with loss-of-function of PC1 or PC2 show higher rates of proliferation and apoptosis and reduced autophagy. PC1 is a large multifunctional transmembrane protein that serves as a sensor that is usually found in complex with PC2, a calcium (Ca)-permeable cation channel. In addition to decreased Ca signaling, several other cell fate-related pathways are de-regulated in ADPKD, including cAMP, MAPK, Wnt, JAK-STAT, Hippo, Src, and mTOR. In this review we discuss how polycystins regulate cell death and survival, highlighting the complexity of molecular cascades that are involved in ADPKD.
摘要
多囊蛋白-1（PC1）和多囊蛋白-2（PC2）的突变导致一种常见的遗传疾病，称为常染色体显性多囊肾病（ADPKD），其特征是肾脏囊肿的形成和发展。丧失 PC1 或 PC2 功能的上皮细胞表现出更高的增殖和凋亡率，以及更低的自噬水平。PC1 是一种大型多功能跨膜蛋白，作为一种传感器，通常与钙（Ca）可渗透的阳离子通道 PC2 形成复合物。除了钙信号降低外，ADPKD 中还有几个其他与细胞命运相关的途径被失调，包括 cAMP、MAPK、Wnt、JAK-STAT、Hippo、Src 和 mTOR。在这篇综述中，我们讨论了多囊蛋白如何调节细胞死亡和存活，强调了参与 ADPKD 的分子级联的复杂性。
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