title: The (pro)renin receptor. A decade of research: what have we learned?
abstract: The discovery of a (pro)renin receptor ((P)RR) in 2002 provided a long-sought explanation for tissue renin-angiotensin system (RAS) activity and a function for circulating prorenin, the inactive precursor of renin, in end-organ damage. Binding of renin and prorenin (referred to as (pro)renin) to the (P)RR increases angiotensin I formation and induces intracellular signalling, resulting in the production of profibrotic factors. However, the (pro)renin concentrations required for intracellular signalling in vitro are several orders of magnitude above (patho)physiological plasma levels. Moreover, the phenotype of prorenin-overexpressing animals could be completely attributed to angiotensin generation, possibly even without the need for a receptor. The efficacy of the only available putative (pro)renin receptor blocker handle region peptide remains doubtful, leading to inconclusive results. The fact that, in contrast to other RAS components, (P)RR knock-outs, even tissue-specific, are lethal, points to an important, (pro)renin-independent, function of the (P)RR. Indeed, recent research has highlighted ancillary functions of the (P)RR as an essential accessory protein of the vacuolar-type H(+)-ATPase (V-ATPase), and in this role, it acts as an intermediate in Wnt signalling independent of (pro)renin. In conclusion, (pro)renin-dependent signalling is unlikely in non-(pro)renin synthesizing organs, and the (P)RR role in V-ATPase integrity and Wnt signalling may explain some, if not all of the phenotypes previously associated with (pro)renin-(P)RR interaction.
authors.affiliation: Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Manne
authors.initials: M
authors.lastname: Krop
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lu
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Marcel E
authors.initials: ME
authors.lastname: Meima
mesh_terms: D000818:Animals; D006801:Humans; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism; D060449:Wnt Signaling Pathway; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor