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Related Experiment Videos

Renin/prorenin receptors.

G Nguyen1

  • 1Institut National de la Santé et de la Recherche Médicale, INSERM Unit 36, Collège de France, Unit of Experimental Medicine, Paris, France. genevieve.nguyen@college-de-france.fr

Kidney International
|May 5, 2006
PubMed
Summary
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Two receptors, M6P-R and a specific receptor, bind renin and prorenin, influencing tissue RAS activity. The specific receptor activates signaling pathways and increases enzyme activity, independent of angiotensin II.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Physiology

Background:

  • The tissue renin-angiotensin system (RAS) operates independently of circulating RAS, necessitating identification of cellular binding sites for renin and angiotensinogen.
  • Understanding tissue uptake mechanisms is crucial for explaining local RAS activity.

Purpose of the Study:

  • To identify and characterize cellular receptors for renin and prorenin.
  • To elucidate the functional consequences of (pro)renin binding to these receptors.
  • To investigate the role of these receptors in cardiovascular and renal diseases.

Main Methods:

  • Identification and characterization of two distinct receptors binding mature renin and prorenin.
  • Analysis of receptor-mediated internalization, degradation, and enzymatic activity.

Related Experiment Videos

  • Investigation of signaling pathway activation (MAPK p44/p42) upon receptor binding.
  • Utilizing experimental rat models with targeted receptor overexpression.

    • Main Results:

    • Two receptors identified: Mannose-6-phosphate Receptor (M6P-R) and a specific (pro)renin receptor.
    • M6P-R acts as a clearance receptor, mediating degradation of glycosylated (pro)renin without intracellular angiotensin generation.
    • The specific receptor binds (pro)renin, enhancing its catalytic activity via conformational changes and activating MAPK p44/p42, independent of angiotensin II.
    • Overexpression of the specific receptor in rats led to hypertension, glomerulosclerosis, and proteinuria.

    Conclusions:

    • The specific (pro)renin receptor explains the presence of active prorenin in vivo and its role in conditions like diabetes with low renin/high prorenin.
    • This receptor mediates critical angiotensin II-independent effects of (pro)renin.
    • The receptor plays a significant role in the pathogenesis of cardiovascular and renal diseases.