Institute of Physiology, University Medicine of Greifswald, Greifswalder Str. 11 C, 17495, Karlsburg, Germany.
Pflugers Arch. 2017 Oct;469(10):1245-1256. doi: 10.1007/s00424-017-2005-z. Epub 2017 Jun 15.
The prorenin receptor was originally discovered as a receptor that binds renin and prorenin, thereby inducing pro-fibrotic intracellular signal cascades. These effects are partially mediated in vitro by angiotensin (ANG) and partially independent of ANG. Consequently, inhibitors of the interaction between the prorenin and the (pro)renin receptor (PRR) were designed hoping that they may prevent fibrotic tissue damage, for instance, in the kidney. However, this concept was challenged by the fact that overexpression of the PRR was not harmful at all, whereas depletion of the PRR was lethal or markedly detrimental. Furthermore, the high levels of prorenin needed to activate the PRR may not be reached in vivo. As it turned out, the PRR instead exhibited a variety of important functions that has nothing to do with the name given to the protein. Thus, the PRR was identified as an accessory subunit of vesicular (v)-ATPases, representing an essential chaperon for the assembly of v-ATPase subunits. In this respect, the gene encoding the PRR was also named ATP6AP2. Finally, the PRR is an essential component of the canonical and non-canonical PCP Wnt pathways. Thus, the PRR is essential for lysosomal functions, such as endocytosis, secretion, and autophagy as well as for cell division and differentiation, embryonic development, organogenesis, and stem cell biology.
原肾素受体最初被发现是一种与肾素和前肾素结合的受体，从而诱导促纤维化的细胞内信号级联反应。这些作用部分在体外通过血管紧张素 (ANG) 介导，部分独立于 ANG。因此，设计了原肾素与（前）肾素受体 (PRR) 相互作用的抑制剂，希望它们可以预防纤维化组织损伤，例如在肾脏中。然而，这一概念受到了挑战，因为 PRR 的过表达根本没有危害，而 PRR 的耗竭则是致命的或明显有害的。此外，体内可能无法达到激活 PRR 所需的高浓度前肾素。事实证明，PRR 反而表现出多种与该蛋白名称无关的重要功能。因此，PRR 被鉴定为囊泡 (v)-ATP 酶的辅助亚基，是 v-ATP 酶亚基组装所必需的伴侣。在这方面，编码 PRR 的基因也被命名为 ATP6AP2。最后，PRR 是经典和非经典 PCP Wnt 途径的必需组成部分。因此，PRR 对于溶酶体功能（如内吞作用、分泌和自噬）以及细胞分裂和分化、胚胎发育、器官发生和干细胞生物学至关重要。
