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The (pro)renin receptor: what’s in a name?

Nature Reviews Nephrology volume 16, page 304 (2020)Cite this article

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We read with interest the recent Review by A. Ichihara and M. S. Yatabe (The (pro)renin receptor in health and disease. Nat. Rev. Nephrol. 15, 693–712 (2019))1. The (pro)renin receptor (PRR; also known as ATP6AP2) was first discovered in 1998 in a biochemical purification approach that yielded a 8.9 kDa fragment of a membrane-associated protein. This fragment associated with the proton pump V-ATPase and was hence given the gene name ATP6AP2 (ref.2). However, in 2002, a seminal paper by Nguyen and colleagues3 suggested that the fragment belonged to a larger protein — the PRR — that can bind to prorenin, the precursor of renin, on the cell surface, thereby facilitating its processing to renin. The circulatory levels of renin are normally ten times lower than those of prorenin. Moreover, elevated prorenin levels correlate with the microvascular complications of diabetes and hypertension, suggesting that prorenin may contribute to the extra-renal effects of renin. The PRR therefore represented a promising drug target to prevent end-organ damage mediated by the renin–angiotensin system (RAS). As a result, the PRR attracted a lot of attention, which was aided to a large extent by its flashy name.

Despite almost two decades of PRR research, it is still far from clear how prorenin is processed and, most importantly, whether this processing is physiologically relevant for the RAS. Unlike previous reviews of this research area4,5, the article by Ichihara and Yatabe1 and another recent review by N. Ramkumar and D. E. Kohan published in Kidney International6 do not acknowledge this uncertainty.

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Authors and Affiliations

  1. INSERM UMR1163, Laboratory of Epithelial Biology and Disease, Imagine Institute, Paris Descartes University, Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, Paris, France

    Matias Simons

  2. Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Germany

    Matias Simons

  3. Max-Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany

    Michael Bader & Dominik N. Müller

  4. University of Lübeck, Institute for Biology, Lübeck, Germany

    Michael Bader

  5. Charité-Universitätsmedizin Berlin, Berlin, Germany

    Michael Bader

  6. German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany

    Michael Bader & Dominik N. Müller

  7. Experimental and Clinical Research Center, a joint cooperation of Max-Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, Berlin, Germany

    Dominik N. Müller

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Correspondence to Matias Simons.

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Simons, M., Bader, M. & Müller, D.N. The (pro)renin receptor: what’s in a name?. Nat Rev Nephrol 16, 304 (2020). https://doi.org/10.1038/s41581-020-0274-9

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