Ichihara Atsuhiro
Department of Medicine II, Endocrinology and Hypertension, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Keio J Med. 2012;61(3):73-8. doi: 10.2302/kjm.61.73.
The (pro)renin receptor [(P)RR] is a molecule that binds prorenin and renin in tissues, leading not only to their activation, but also carrying out intracellular signaling. As a key player in the tissue renin-angiotensin system, (P)RR activation plays an important role in the development of end-organ damage in hypertension and diabetes. One fragment of (P)RR is also known as ATP6AP2 because it is associated with vacuolar H(+)-ATPase (V-ATPase). V-ATPase is a multi-subunit proton pump involved in diverse and fundamental aspects of cellular physiology, including receptor-mediated endocytosis and recycling, processing of proteins and signaling molecules, membrane sorting and trafficking, and activation of lysosomal/autophagosomal enzymes. The role of (P)RR in the function of V-ATPase has been investigated in recent studies using conditional knockout mice. Furthermore, the novel function of (P)RR as an adaptor protein between the Wnt receptor complex and V-ATPase has been demonstrated. Thus, (P)RR is a multi-functional molecule that has complex structure and functionality. This review focuses on current insights into the possibility of (P)RR acting as a modulator of V-ATPase and future perspectives in translational research.
(前)肾素受体[(P)RR]是一种在组织中结合肾素原和肾素的分子,不仅能导致它们的激活,还能进行细胞内信号传导。作为组织肾素 - 血管紧张素系统中的关键分子,(P)RR激活在高血压和糖尿病终末器官损伤的发展中起重要作用。(P)RR的一个片段也被称为ATP6AP2,因为它与液泡H(+) - ATP酶(V - ATP酶)相关。V - ATP酶是一种多亚基质子泵,参与细胞生理学的多种基本过程,包括受体介导的内吞作用和再循环、蛋白质和信号分子的加工、膜分选和运输以及溶酶体/自噬体酶的激活。最近使用条件性基因敲除小鼠的研究对(P)RR在V - ATP酶功能中的作用进行了研究。此外,还证明了(P)RR作为Wnt受体复合物和V - ATP酶之间衔接蛋白的新功能。因此,(P)RR是一种具有复杂结构和功能的多功能分子。本综述重点关注对(P)RR作为V - ATP酶调节剂可能性的当前见解以及转化研究的未来前景。