Renin/prorenin-receptor biochemistry and functional significance
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Updated: Aug 25, 2026

Receptor Autoradiography Protocol for the Localized Visualization of Angiotensin II Receptors
Published on: June 7, 2016
Geneviève Nguyen1, Céline A Burcklé, Jean-Daniel Sraer
1INSERM U36, Collège de France, 11, place Marcelin Berthelot, 75005, Paris, France. genevieve.nguyen@college-de-france.fr
Abstract:
The renin-angiotensin system (RAS) has become increasingly complex. New components have been identified, and additional roles for angiotensin peptides and their receptors are being uncovered. A functional (pro)renin receptor has been cloned that acts as (pro)renin cofactor on cell surface, enhancing the efficiency of angiotensinogen cleavage by (pro)renin and unmasking prorenin catalytic activity. Binding of (pro)renin to the receptor mediates (pro)renin cellular effects by activating mitogen-activating protein (MAP) kinases, extracellular signal-regulated kinases (ERK)1/2. Immunofluorescence studies have localized the receptor on mesangial and vascular smooth muscle cells in human heart and kidney. This suggests that the renin receptor might represent a means to capture (pro)renin from the circulation and to concentrate (pro)renin at the interface between smooth muscle and endothelial cells. In this article, we review the biochemical characteristics of this receptor and of other renin-binding proteins, and discuss their physiologic significance.
Insights
A newly identified (pro)renin receptor acts as a cofactor, enhancing angiotensinogen cleavage and mediating cellular effects via MAP kinases. This receptor is found in human heart and kidney, suggesting roles in regulating the renin-angiotensin system.
Area of Science:
- Molecular Biology
- Cardiovascular Physiology
- Renal Physiology
Background:
- The renin-angiotensin system (RAS) is complex, with newly identified components and roles for angiotensin peptides.
- Understanding the RAS is crucial for cardiovascular and renal health.
Purpose of the Study:
- To review the biochemical characteristics of the functional (pro)renin receptor and other renin-binding proteins.
- To discuss the physiological significance of the (pro)renin receptor in the renin-angiotensin system.
Main Methods:
- Cloning of a functional (pro)renin receptor.
- Investigation of the receptor's cofactor activity in angiotensinogen cleavage.
- Analysis of receptor-mediated cellular signaling pathways, including MAP kinases (ERK1/2).
- Immunofluorescence studies to determine receptor localization in human tissues.
Main Results:
- A functional (pro)renin receptor was cloned, acting as a cell surface cofactor for (pro)renin.
- The receptor enhances angiotensinogen cleavage and unmasks prorenin's catalytic activity.
- Binding to the receptor activates MAP kinases (ERK1/2), mediating cellular effects.
- The receptor is localized on mesangial and vascular smooth muscle cells in the human heart and kidney.
Conclusions:
- The (pro)renin receptor plays a significant role in the renin-angiotensin system's complexity.
- Its localization suggests a mechanism for capturing and concentrating (pro)renin in specific cellular environments.
- Further understanding of this receptor and related proteins is vital for elucidating RAS physiology.
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