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Angiotensin (1-7) induces MAS receptor internalization
Mariela M Gironacci1, Hugo P Adamo, Gerardo Corradi
1Instituto de Química y Fisicoquímica Biológicas, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 1113 Buenos Aires, Argentina. mariela@qb.ffyb.uba.ar
Angiotensin (1-7) binding causes the Mas receptor to internalize into cells, which may explain its desensitization. This cellular process helps regulate Mas receptor activity and density.
Area of Science:
- Cell Biology
- Molecular Pharmacology
- Cardiovascular Physiology
Background:
- The Mas receptor (MasR), activated by Angiotensin (1-7), is crucial for protective responses in the heart, kidneys, and brain.
- Agonist-dependent desensitization of MasR is suggested physiologically, but the molecular mechanisms remain unclear.
Purpose of the Study:
- To investigate if MasR desensitizes and internalizes upon stimulation with Angiotensin (1-7).
- To elucidate the molecular pathway of MasR internalization.
Main Methods:
- A MasR-yellow fluorescent protein (YFP) chimera was created and expressed in HEK 293T cells.
- Confocal microscopy was used to track MasR-YFP localization after Angiotensin (1-7) stimulation.
- Radioligand endocytosis assays and colocalization studies with endosomal markers (Rab5, EEA1, AP2, caveolin 1) were performed.
Main Results:
- Angiotensin (1-7) stimulation induced rapid redistribution of MasR-YFP from the cell membrane to intracellular vesicles.
- Half of MasR-YFP underwent endocytosis within 10 minutes, a process blocked by a MasR antagonist.
- MasR-YFP internalization occurred via a clathrin-mediated pathway, targeting early endosomes and potentially caveolin 1-positive compartments.
Conclusions:
- MasR undergoes endocytosis in response to Angiotensin (1-7) stimulation.
- This endocytic process is a likely mechanism for MasR desensitization.
- Cellular internalization provides a means to tightly regulate MasR activity and surface expression.
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