Institut National de la Santé et de la Recherche Médicale (INSERM) and Collège de France Early Development and Pathologies Center for Interdisciplinary Research in Biology and Experimental Medicine Unit, 11 place Marcelin Berthelot, 75005, Paris, France.
Clin Sci (Lond). 2011 Mar;120(5):169-78. doi: 10.1042/CS20100432.
PRR [(pro)renin receptor] was named after its biological characteristics, namely the binding of renin and of its inactive precursor prorenin, that triggers intracellular signalling involving ERK (extracellular-signal-regulated kinase) 1/2. However the gene encoding for PRR is named ATP6ap2 (ATPase 6 accessory protein 2) because PRR was initially found as a truncated form co-purifying with V-ATPase (vacuolar H+-ATPase). There are now data showing that this interaction is not only physical, but also functional in the kidney and the heart. However, the newest and most fascinating development of PRR is its involvement in both the canonical Wnt/β-catenin and non-canonical Wnt/PCP (planar cell polarity) pathways, which are essential for adult and embryonic stem cell biology, embryonic development and disease, including cancer. In the Wnt/β-catenin pathway, it has been shown that PRR acts as an adaptor between the Wnt receptor LRP5/6 (low-density lipoprotein receptor-related protein 5/6) and Fz (frizzled) and that the proton gradient generated by the V-ATPase in endosomes is necessary for LRP5/6 phosphorylation and β-catenin activation. In the Wnt/PCP pathway, PRR binds to Fz and controls its asymetrical subcellular distribution and therefore the polarization of the cells in a plane of a tissue. These essential cellular functions of PRR are independent of renin and open new avenues on the pathophysiological role of PRR. The present review will summarize our knowledge of (pro)renin-dependent functions of PRR and will discuss the newly recognized functions of PRR related to the V-ATPase and to Wnt signalling.
PRR[(前肾素受体)]因其生物学特性而得名，即与肾素及其无活性前体原肾素结合，触发涉及 ERK(细胞外信号调节激酶)1/2 的细胞内信号转导。然而，编码 PRR 的基因被命名为 ATP6ap2(ATP 酶 6 辅助蛋白 2)，因为 PRR 最初被发现是与 V-ATPase(液泡 H+-ATP 酶)共纯化的截断形式。现在有数据表明，这种相互作用不仅是物理的，而且在肾脏和心脏中也是功能性的。然而，PRR 的最新和最迷人的发展是它参与经典的 Wnt/β-连环蛋白和非经典的 Wnt/PCP(平面细胞极性)途径，这对于成体和胚胎干细胞生物学、胚胎发育和疾病，包括癌症，是必不可少的。在 Wnt/β-连环蛋白途径中，已经表明 PRR 作为 Wnt 受体 LRP5/6(低密度脂蛋白受体相关蛋白 5/6)和 Fz(frizzled)之间的衔接物起作用，并且内体中 V-ATPase 产生的质子梯度对于 LRP5/6 磷酸化和 β-连环蛋白激活是必要的。在 Wnt/PCP 途径中，PRR 与 Fz 结合并控制其不对称的亚细胞分布，从而控制细胞在组织平面中的极化。PRR 的这些基本细胞功能独立于肾素，并为 PRR 的病理生理学作用开辟了新的途径。本综述将总结我们对 PRR 依赖于前肾素的功能的认识，并将讨论与 V-ATPase 和 Wnt 信号相关的新发现的 PRR 功能。
