Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin

Nguyen, Geneviève; Delarue, F; Burcklé, Céline; Bouzhir, Latifa; Giller, Thomas; Sraër, Jean-Daniel

doi:10.1172/jci200214276

Cited by 97 publications

(3 citation statements)

References 33 publications

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“…Analysis of the concentrations of Renin vs. Prorenin circulating in the blood has suggested upwards of a 10 fold higher level of Prorenin, implicating potential tissue specific roles of prorenin activation by PRR (Zhuo, 2011). In addition, Prorenin binding to PRR activates intracellular pathways such as ERK 1/2 with proposed roles in cranial RAS signaling (Nguyen, 2011; Nguyen et al, 2002). The process of activation of Renin and the impact of oxidized and reduced AGT can be seen at https://www.youtube.com/watch?v=RsEEs5WFkSQ&feature=youtu.be.…”

Section: Introductionmentioning

confidence: 99%

Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system

Prokop

Petri

Shimoyama

et al. 2015

General and Comparative Endocrinology

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The details of protein pathways at a structural level provides a bridge between genetics/molecular biology and physiology. The renin-angiotensin system is involved in many physiological pathways with informative structural details in multiple components. Few studies have been performed assessing structural knowledge across the system. This assessment allows use of bioinformatics tools to fill in missing structural voids. In this paper we detail known structures of the renin-angiotensin system and use computational approaches to estimate and model components that do not have their protein structures defined. With the subsequent large library of protein structures, we then created a species specific protein library for human, mouse, rat, bovine, zebrafish, and chicken for the system. The rat structural system allowed for rapid screening of genetic variants from 51 commonly used rat strains, identifying amino acid variants in Angiotensinogen, ACE2, and AT1b that are in contact positions with other macromolecules. We believe the structural map will be of value for other researchers to understand their experimental data in the context of an environment for multiple proteins, providing pdb files of proteins for the renin-angiotensin system in six species. With detailed structural descriptions of each protein, it is easier to assess a species for use in translating human diseases with animal models. Additionally, as whole genome sequencing continues to decrease in cost, tools such as molecular modeling will gain use as an initial step in designing efficient hypothesis driven research, addressing potential functional outcomes of genetic variants with precompiled protein libraries aiding in rapid characterizations.

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Section: Introductionmentioning

confidence: 99%

Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system

Prokop

Petri

Shimoyama

et al. 2015

General and Comparative Endocrinology

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Section: Introductionmentioning

confidence: 99%

“…In addition, renin has been recently recognized as a signaling molecule as well [2]. Binding to its receptor, both renin and prorenin lead to an intracellular signaling process associated with ERK 1/2 activation [2]. As the rate-limiting step of RAS activation, renin release from JG cells in the terminal afferent arteriole is fastidiously controlled by many mechanisms [3, 4].…”

Section: Introductionmentioning

confidence: 99%

Imaging Renin Content and Release in the Living Kidney

Toma

Kang²,

Peti‐Peterdi³

2006

Nephron Physiol

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Renin release is the first, and at least initially, the rate-limiting step in the activation of the renin-angiotensin system, which helps to maintain body salt and water balance. Recent advances in our understanding of pathophysiology have generated a renewed interest in the multiple roles of renin and prorenin as a hormone, enzyme, and signaling molecule. The assays available to measure renin content, release and tissue activity are complex, indirect and work with significant internal errors. We developed an imaging approach to directly visualize renin content and study the dynamics of both the release and tissue activity of renin. Our experimental model uses multiphoton fluorescence microscopy, which is ideal for deep optical sectioning of the living renal tissue. Here we review the application of this renin imaging approach to the dissected, in vitro microperfused glomerulus as well as in the intact kidney in vivo.

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Cardiac (Pro)Renin Receptors: Functional Properties and Potential Significance

Nguyen

Danser

2006

Basic Science for the Cardiologist

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In many tissues, local angiotensin generation depends on uptake of circulating renin andlor prorenin. Such uptake involves both diffusion into the interstitial space and binding to (pro)renin receptors. This review describes the current status of cardiac (pro)renin receptors, and focusses on their potential significance. (Pro)renin receptors bind both renin and prorenin, and prorenin undergoes a confonnational change ('non-proteolytic' activation) following binding, thereby allowing cell surface angiotensin generation with both renin and prorenin. Renin and prorenin binding also induced direct, angiotensinindependent effects (e.g., ERK112 activation), suggesting that renin and prorenin may act as agonists. Finally, under certain conditions binding resulted in internalization of renin and prorenin. Internalized renin and prorenin were either degraded or, in the case of unglycosylated prorenin, contributed to intracellular angiotensin generation. Taken together, (pro)renin receptors could provide an important new drug target, allowing selective interference with angiotensin production at tissues sites andor direct (pro)renin-induced effects.

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Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin

Cited by 97 publications

References 33 publications

Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system

Structural libraries of protein models for multiple species to understand evolution of the renin-angiotensin system

Imaging Renin Content and Release in the Living Kidney

Cardiac (Pro)Renin Receptors: Functional Properties and Potential Significance

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