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Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS

Overview of attention for article published in Hypertension, May 2017
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Title
Evidence for Heterodimerization and Functional Interaction of the Angiotensin Type 2 Receptor and the Receptor MAS
Published in
Hypertension, May 2017
DOI 10.1161/hypertensionaha.116.08814
Pubmed ID
Authors

Julia Leonhardt, Daniel C Villela, Anke Teichmann, Lisa-Marie Münter, Magnus C Mayer, Maibritt Mardahl, Sebastian Kirsch, Pawel Namsolleck, Kristin Lucht, Verena Benz, Natalia Alenina, Nicholas Daniell, Masatsugu Horiuchi, Masaru Iwai, Gerhard Multhaup, Ralf Schülein, Michael Bader, Robson A Santos, Thomas Unger, Ulrike Muscha Steckelings

Abstract

The angiotensin type 2 receptor (AT2R) and the receptor MAS are receptors of the protective arm of the renin-angiotensin system. They mediate strikingly similar actions. Moreover, in various studies, AT2R antagonists blocked the effects of MAS agonists and vice versa. Such cross-inhibition may indicate heterodimerization of these receptors. Therefore, this study investigated the molecular and functional interplay between MAS and the AT2R. Molecular interactions were assessed by fluorescence resonance energy transfer and by cross correlation spectroscopy in human embryonic kidney-293 cells transfected with vectors encoding fluorophore-tagged MAS or AT2R. Functional interaction of AT2R and MAS was studied in astrocytes with CX3C chemokine receptor-1 messenger RNA expression as readout. Coexpression of fluorophore-tagged AT2R and MAS resulted in a fluorescence resonance energy transfer efficiency of 10.8 ± 0.8%, indicating that AT2R and MAS are capable to form heterodimers. Heterodimerization was verified by competition experiments using untagged AT2R and MAS. Specificity of dimerization of AT2R and MAS was supported by lack of dimerization with the transient receptor potential cation channel, subfamily C-member 6. Dimerization of the AT2R was abolished when it was mutated at cysteine residue 35. AT2R and MAS stimulation with the respective agonists, Compound 21 or angiotensin-(1-7), significantly induced CX3C chemokine receptor-1 messenger RNA expression. Effects of each agonist were blocked by an AT2R antagonist (PD123319) and also by a MAS antagonist (A-779). Knockout of a single of these receptors made astrocytes unresponsive for both agonists. Our results suggest that MAS and the AT2R form heterodimers and that-at least in astrocytes-both receptors functionally depend on each other.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 71 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 71 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 13%
Professor 9 13%
Student > Master 9 13%
Student > Bachelor 7 10%
Researcher 7 10%
Other 11 15%
Unknown 19 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 10 14%
Agricultural and Biological Sciences 10 14%
Medicine and Dentistry 9 13%
Pharmacology, Toxicology and Pharmaceutical Science 8 11%
Chemistry 6 8%
Other 8 11%
Unknown 20 28%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 May 2017.
All research outputs
#16,725,651
of 25,382,440 outputs
Outputs from Hypertension
#5,285
of 7,141 outputs
Outputs of similar age
#196,441
of 324,557 outputs
Outputs of similar age from Hypertension
#54
of 84 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,141 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one is in the 24th percentile – i.e., 24% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 324,557 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.