Renin, (pro)renin and receptor: an update.

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• The (pro)renin receptor (PRR), encoded by ATP6ap2, was initially identified through its interaction with vacuolar H+-ATPase (V-ATPase).
• PRR binds renin and prorenin, initiating intracellular signaling cascades like ERK1/2 activation.
• PRR's physical and functional interaction with V-ATPase is established in kidney and heart tissues.

Purpose of the Study:

• To review the known (pro)renin-dependent functions of PRR.
• To discuss the newly identified roles of PRR concerning V-ATPase and Wnt signaling.
• To explore the pathophysiological implications of PRR's novel functions.

Main Methods:

• Literature review of studies on PRR, V-ATPase, and Wnt signaling pathways.
• Analysis of experimental data linking PRR to canonical and non-canonical Wnt pathways.
• Synthesis of current knowledge on PRR's independent roles in cellular processes.

Main Results:

• PRR acts as an adaptor in the Wnt/β-catenin pathway, facilitating LRP5/6 phosphorylation and β-catenin activation via V-ATPase-generated proton gradients.
• In the Wnt/PCP pathway, PRR regulates Frizzled (Fz) distribution, influencing cell polarization.
• These Wnt pathway functions of PRR are independent of its interaction with renin.

Conclusions:

• PRR possesses critical functions in Wnt/β-catenin and Wnt/PCP signaling pathways, essential for stem cell biology and development.
• PRR's interaction with V-ATPase is functionally significant, particularly in Wnt pathway regulation.
• The renin-independent roles of PRR open new perspectives on its involvement in disease pathogenesis, including cancer.