| Title |
Brag2 differentially regulates β1- and β3-integrin-dependent adhesion in endothelial cells and is involved in developmental and pathological angiogenesis
|
|---|---|
| Published in |
Basic Research in Cardiology, February 2014
|
| DOI | 10.1007/s00395-014-0404-2 |
| Pubmed ID | |
| Authors |
Yosif Manavski, Guillaume Carmona, Katrin Bennewitz, Zhongshu Tang, Fan Zhang, Atsuko Sakurai, Andreas M. Zeiher, J. Silvio Gutkind, Xuri Li, Jens Kroll, Stefanie Dimmeler, Emmanouil Chavakis |
| Abstract |
β1-Integrins are essential for angiogenesis. The mechanisms regulating integrin function in endothelial cells (EC) and their contribution to angiogenesis remain elusive. Brag2 is a guanine nucleotide exchange factor for the small Arf-GTPases Arf5 and Arf6. The role of Brag2 in EC and angiogenesis and the underlying molecular mechanisms remain unclear. siRNA-mediated Brag2-silencing reduced EC angiogenic sprouting and migration. Brag2-siRNA transfection differentially affected α5β1- and αVβ3-integrin function: specifically, Brag2-silencing increased focal/fibrillar adhesions and adhesion on β1-integrin ligands (fibronectin and collagen), while reducing the adhesion on the αVβ3-integrin ligand, vitronectin. Consistent with these results, Brag2-silencing enhanced surface expression of α5β1-integrin, while reducing surface expression of αVβ3-integrin. Mechanistically, Brag2-mediated αVβ3-integrin-recycling and β1-integrin endocytosis and specifically of the active/matrix-bound α5β1-integrin present in fibrillar/focal adhesions (FA), suggesting that Brag2 contributes to the disassembly of FA via β1-integrin endocytosis. Arf5 and Arf6 are promoting downstream of Brag2 angiogenic sprouting, β1-integrin endocytosis and the regulation of FA. In vivo silencing of the Brag2-orthologues in zebrafish embryos using morpholinos perturbed vascular development. Furthermore, in vivo intravitreal injection of plasmids containing Brag2-shRNA reduced pathological ischemia-induced retinal and choroidal neovascularization. These data reveal that Brag2 is essential for developmental and pathological angiogenesis by promoting EC sprouting through regulation of adhesion by mediating β1-integrin internalization and link for the first time the process of β1-integrin endocytosis with angiogenesis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Members of the public | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 3% |
| Unknown | 31 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 28% |
| Researcher | 7 | 22% |
| Student > Doctoral Student | 4 | 13% |
| Student > Master | 3 | 9% |
| Professor | 2 | 6% |
| Other | 5 | 16% |
| Unknown | 2 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 11 | 34% |
| Biochemistry, Genetics and Molecular Biology | 9 | 28% |
| Medicine and Dentistry | 7 | 22% |
| Neuroscience | 2 | 6% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
| Other | 0 | 0% |
| Unknown | 2 | 6% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 23 January 2020.
All research outputs
#4,437,334
of 22,745,803 outputs
Outputs from Basic Research in Cardiology
#74
of 644 outputs
Outputs of similar age
#55,813
of 313,457 outputs
Outputs of similar age from Basic Research in Cardiology
#2
of 4 outputs
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So far Altmetric has tracked 644 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has done well, scoring higher than 88% of its peers.
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