Autophagy and the (Pro)renin Receptor.
Autophagy and the (Pro)renin Receptor.
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DOI：
10.3389/fendo.2013.00155
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发表时间：
2013-10-21
影响因子：
5.2
通讯作者：
Muller DN
中科院分区：
文献类型：
--
作者：
Binger KJ;Muller DN
原肾素受体（PRR）是新近报道的肾素-血管紧张素系统（RAS）的成员，是一种负责调节血压的激素级联反应。最初，PRR的鉴定被认为是RAS的下一个药物靶点，其中这种疗法将增加对靶器官损伤和高血压的益处。然而，在其发现以来的几年中，PRR的几个条件性敲除小鼠模型已经证明了这种受体与RAS和血压无关的重要作用。在足细胞或心肌细胞中特异性缺失PRR导致器官衰竭的快速发作，随后仅在几周后动物死亡。在这两种细胞类型中，PRR的丧失导致自噬体和错误折叠蛋白质的细胞内积累，表明自噬紊乱。鉴于大多数PRR位于细胞内的事实，这种分子功能似乎比其结合高的非生理浓度的（原）肾素的能力更相关。本文就PRR在自噬中的作用及其在维持细胞内稳态中的重要性作一综述。了解PRR，自噬及其损失如何导致细胞死亡之间的联系对于破译其在生理学和病理学中的作用至关重要。
The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.