MAS1 Receptor Trafficking Involves ERK1/2 Activation Through a β-Arrestin2-Dependent Pathway.

Area of Science:

• Pharmacology
• Cell Biology
• Molecular Biology

Background:

• The MAS1 receptor (R) plays a protective role in various organs, including the brain, heart, vessels, and kidney.
• Receptor trafficking is crucial for signal termination, propagation, and resensitization.
• Understanding MAS1R trafficking and signaling pathways is essential for its therapeutic potential.

Purpose of the Study:

• To investigate MAS1R internalization and trafficking mechanisms following agonist stimulation.
• To elucidate the role of β-arrestin2 in MAS1R-mediated activation of ERK1/2 and Akt signaling pathways.

Main Methods:

• Human embryonic kidney 293T cells expressing MAS1R-YFP were used.
• MAS1R internalization was assessed via ligand-binding assays.
• Trafficking was evaluated by colocalization with specific markers; signaling pathways were analyzed using knockdown approaches.

Main Results:

• MAS1R internalization was dependent on clathrin-coated pits, caveolae, and dynamin.
• Following stimulation, MAS1R colocalized with Rab11 (slow recycling) but not Rab4 or LysoTracker.
• Angiotensin-(1-7) stimulation increased Akt and ERK1/2 activation, with ERK1/2 activation reduced by β-arrestin2 suppression.

Conclusions:

• MAS1R undergoes clathrin- and caveolae-mediated, dynamin-dependent internalization and slow recycling.
• MAS1R signals through early endosomes to activate Akt and ERK1/2.
• β-arrestin2 specifically mediates angiotensin-(1-7)-induced ERK1/2 activation, highlighting a regulatory mechanism for MAS1R signaling.