Renin/prorenin-receptor biochemistry and functional significance

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

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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