Renin, (pro)renin and receptor: an update

Abstract

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.

Water Deprivation Increases (Pro)renin Receptor Levels in the Kidney and Decreases Plasma Concentrations of Soluble (Pro)renin Receptor

“…(P)RR is expressed, not only in the kidney, but also in various organs including brain (Hirose et al , 2010Takahashi et al 2010a, b;Nguyen 2011). (P)RR was colocalized with vasopressin in the paraventricular and supraoptic neurons of hypothalamus (Takahashi et al 2010a).…”

“…(Pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, is a 350-amino acid protein with a single transmembrane domain (Nguyen et al 2002;Nguyen 2011). The binding of prorenin to (P)RR activates the angiotensin I (Ang I)-generating activity of prorenin, and directly stimulates the intracellular signalling pathways, including extracellular signal-regulated kinase (ERK 1/2) (Nguyen et al 2002;Nguyen 2011).…”

“…The binding of prorenin to (P)RR activates the angiotensin I (Ang I)-generating activity of prorenin, and directly stimulates the intracellular signalling pathways, including extracellular signal-regulated kinase (ERK 1/2) (Nguyen et al 2002;Nguyen 2011). Soluble (P)RR (s(P)RR) comprising of the extracellular domain of (P)RR, and a truncated form of (P)RR at the C-terminal region (truncated (P)RR) are generated from full-length (P)RR (f(P)RR) by furin (Cousin et al 2009;Nguyen 2011). The truncated (P)RR is associated with vacuolar H + -ATPase (v-ATPase), an ATP-dependent multi-subunit proton pump (Ludwig et al 1998).…”

Expression of (pro)renin receptor in breast cancers and its effect on cancercell proliferation

“…with single transmembrane domain (18)(19)(20). Receptor-bound prorenin becomes enzymatically active in converting AGT to Ang I by conformational change.…”

MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

“…In one case, renin secretion by cultured tumor cells was found to be inhibited by 5-HT in a paracrine fashion revealing complex regulations within the tumor tissue (72). The pathophysiological relevance of these findings is not clear but the recent identification of a membrane receptor for renin, which mediates angiogenic and mitogenic actions of the protein through interaction with the Wnt/b-catenin pathway (200,201), could suggest that renin may be involved in adrenocortical tumorigenesis (202,203,204).…”