(Pro)renin Receptor and Vacuolar H+−ATPase

Abstract

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.