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Attention Score in Context
| Title |
Activation of Relaxin Family Receptor 1 from Different Mammalian Species by Relaxin Peptide and Small-Molecule Agonist ML290
|
|---|---|
| Published in |
Frontiers in endocrinology, August 2015
|
| DOI | 10.3389/fendo.2015.00128 |
| Pubmed ID | |
| Authors |
Zaohua Huang, Courtney Myhr, Ross A. D. Bathgate, Brian A. Ho, Amaya Bueno, Xin Hu, Jingbo Xiao, Noel Southall, Elena Barnaeva, Irina U. Agoulnik, Juan J. Marugan, Marc Ferrer, Alexander I. Agoulnik |
| Abstract |
Relaxin peptide (RLN), which signals through the relaxin family peptide 1 (RXFP1) GPCR receptor, has shown therapeutic effects in an acute heart failure clinical trial. We have identified a small-molecule agonist of human RXFP1, ML290; however, it does not activate the mouse receptor. To find a suitable animal model for ML290 testing and to gain mechanistic insights into the interaction of various ligands with RXFP1, we have cloned rhesus macaque, pig, rabbit, and guinea pig RXFP1s and analyzed their activation by RLN and ML290. HEK293T cells expressing macaque or pig RXFP1 responded to relaxin and ML290 treatment as measured by an increase of cAMP production. Guinea pig RXFP1 responded to relaxin but had very low response to ML290 treatment only at highest concentrations used. The rabbit RXFP1 amino acid sequence was the most divergent, with a number of unique substitutions within the ectodomain and the seven-transmembrane domain (7TM). Two splice variants of rabbit RXFP1 derived through alternative splicing of the fourth exon were identified. In contrast to the other species, rabbit RXFP1s were activated by ML290, but not with human, pig, mouse, or rabbit RLNs. Using FLAG-tagged constructs, we have shown that both rabbit RXFP1 variants are expressed on the cell surface. No binding of human Eu-labeled RLN to rabbit RXFP1 was detected, suggesting that in this species, RXFP1 might be non-functional. We used chimeric rabbit-human and guinea pig-human constructs to identify regions important for RLN or ML290 receptor activation. Chimeras with the human ectodomain and rabbit 7TM domain were activated by RLN, whereas substitution of part of the guinea pig 7TM domain with the human sequence only partially restored ML290 activation, confirming the allosteric mode of action for the two ligands. Our data demonstrate that macaque and pig models can be used for ML290 testing. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 4% |
| United States | 1 | 4% |
| Unknown | 24 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 6 | 23% |
| Other | 5 | 19% |
| Student > Ph. D. Student | 4 | 15% |
| Student > Doctoral Student | 2 | 8% |
| Student > Bachelor | 2 | 8% |
| Other | 2 | 8% |
| Unknown | 5 | 19% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 19% |
| Chemistry | 5 | 19% |
| Medicine and Dentistry | 4 | 15% |
| Agricultural and Biological Sciences | 3 | 12% |
| Psychology | 1 | 4% |
| Other | 3 | 12% |
| Unknown | 5 | 19% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. 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 17 August 2015.
All research outputs
#22,758,309
of 25,373,627 outputs
Outputs from Frontiers in endocrinology
#8,332
of 13,012 outputs
Outputs of similar age
#238,040
of 277,786 outputs
Outputs of similar age from Frontiers in endocrinology
#44
of 52 outputs
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So far Altmetric has tracked 13,012 research outputs from this source. They receive a mean Attention Score of 4.9. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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