Toggle Main Menu Toggle Search

Open Access padlockePrints

The (Pro) Renin Receptor Site-Specific and Functional Linkage to the Vacuolar H+-ATPase in the Kidney

Lookup NU author(s): Dr Andrew Advani, Dr Kathryn White, Suzanne Advani


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


The (pro) renin receptor ([P]RR) is a transmembrane protein that binds both renin and prorenin with high affinity, increasing the catalytic cleavage of angiotensinogen and signaling intracellularly through mitogen-activated protein kinase activation. Although initially reported as having no homology with any known membrane protein, other studies have suggested that the (P) RR is an accessory protein, named ATP6ap2, that associates with the vacuolar H+-ATPase, a key mediator of final urinary acidification. Using in situ hybridization, immunohistochemistry, and electron microscopy, together with serial sections stained with nephron segment-specific markers, we found that (P)RR mRNA and protein were predominantly expressed in collecting ducts and in the distal nephron. Within collecting ducts, the (P)RR was most abundant in microvilli at the apical surface of A-type intercalated cells. Dual-staining immunofluorescence demonstrated colocalization of the (P)RR with the B1/2 subunit of the vacuolar H+-ATPase, the ion exchanger that secretes H+ ions into the urinary space and that associates with an accessory subunit homologous to the (P)RR. In collecting duct/distal tubule lineage Madin-Darby canine kidney cells, extracellular signal-regulated kinase 1/2 phosphorylation, induced by either renin or prorenin, was attenuated by the selective vacuolar H+-ATPase inhibitor bafilomycin. The predominant expression of the (P)RR at the apex of acid-secreting cells in the collecting duct, along with its colocalization and homology with an accessory protein of the vacuolar H+-ATPase, suggests that the (P) RR may function primarily in distal nephron H+ transport, recently noted to be, at least in part, an angiotensin II-dependent phenomenon. (Hypertension. 2009; 54: 261-269.)

Publication metadata

Author(s): Advani A, Kelly DJ, Cox AJ, White KE, Advani SL, Thai K, Connelly KA, Yuen D, Trogadis J, Herzenberg AM, Kuliszewski MA, Leong-Poi H, Gilbert RE

Publication type: Article

Publication status: Published

Journal: Hypertension

Year: 2009

Volume: 54

Issue: 2

Pages: 261-U129

ISSN (print): 0194-911X

ISSN (electronic): 1524-4563

Publisher: Hypertension


DOI: 10.1161/HYPERTENSIONAHA.109.128645


Altmetrics provided by Altmetric