# Cloning and characterization of PRR24 as a specific renin receptor critically involved in vasopressin signaling in the kidney

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2024 · $507,643

## Abstract

Summary
(Pro)renin receptor (PRR), a new member of the renin-angiotensin system (RAS), has emerged as a key regulator
of renal handling of Na+ and water, and blood pressure (BP). Renal action of PRR is at least in part mediated
through its ability to activate tissue prorenin and renin. In preliminary studies, investigation of a “non-specific”
protein band recognized by a custom-made anti-PRR antibody has led to identification of a novel 24-kDa isoform
of PRR, termed as PRR24. PRR24 was encoded by a novel cDNA with part of 5’UTR arising from retention of
intron 3 and an ATG in exon 5 as an alternative start codon so that this isoform overlaps completely with PRR
except that N-terminal 136 amino acids are missing. PRR24 expression was predominantly detected in the renal
medulla. PRR24 selectively bound and activated renin but not prorenin whereas PRR non-selectively interacted
both prorenin and renin. In cultured collecting duct (CD) cells, PRR24 translocated from the cytosol to the nucleus
in a cAMP/PKA-dependent manner following vasopressin (AVP) treatment. The trafficking event also occurred
in mouse renal medulla following water deprivation. PRR24 was not only required but also sufficient for
induction of aquaporin-2 (AQP2) transcription induced by AVP. Furthermore, ablation of PRR24 by mutagenesis
of its start codon in mice (termed PRR24mut) induced nephrogenic diabetes insipidus (NDI) associated with
volume contraction and hypotension as well as reduced renal medullary renin activity. Therefore, we hypothesize
that PRR24 serves as a specific renin receptor critically involved in AVP-induced signaling pathway to control
AQP2 transcription and thus urine concentrating capability and plasma volume (Fig. 1). To test this hypothesis,
we will conduct a full panel of phenotypical analysis of PRR24mut mice during perturbation of water balance. In
addition, we will define the transcriptional activity of PRR24 in regulation of AQP2 expression through analysis
of the threonine/threonine sites of PKA-dependent phosphorylation of PRR24 and fine mapping of PRR24-
responsive elements in AQP2 promoter during AVP treatment. Overall, this proposal is expected to offer novel
insight into the function of a newly described PRR24 in the kidney.

## Key facts

- **NIH application ID:** 10835104
- **Project number:** 5R01DK104072-07
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Tianxin Yang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,643
- **Award type:** 5
- **Project period:** 2015-02-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835104

## Citation

> US National Institutes of Health, RePORTER application 10835104, Cloning and characterization of PRR24 as a specific renin receptor critically involved in vasopressin signaling in the kidney (5R01DK104072-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10835104. Licensed CC0.

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