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Open AccessArticle

Rap1 is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting

Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada
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Cells 2020, 9(1), 155; https://doi.org/10.3390/cells9010155
Received: 22 November 2019 / Revised: 27 December 2019 / Accepted: 4 January 2020 / Published: 8 January 2020
(This article belongs to the Special Issue Angiopoietin Signaling)
Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical for endothelial cell–cell adhesions, its roles in the antipermeability effects of Ang-1 are ill-defined. Thus, we determined the contribution of Rap1 to Ang-1-stimulated angiogenic effects on endothelial cells (ECs). We found that Rap1 is activated following Ang-1 stimulation and is required for the antipermeability effects of Ang-1 on EC monolayers. Our results also revealed that Rap1 is necessary for EC sprouting stimulated by Ang-1 but had no significant effect on Ang-1-induced EC migration and adhesion. In contrast, downregulation of VE-cadherin markedly increased the adhesiveness of ECs to the substratum, which resulted in inhibition of Ang-1-stimulated migration. These results revealed that Rap1 is central to the effects of Ang-1 at intercellular junctions of ECs, whereas VE-cadherin is also involved in the adhesion of ECs to the extracellular matrix.
Keywords: angiopoietin-1; angiogenesis; Rap1; VE-cadherin; migration; adhesion; endothelial cells angiopoietin-1; angiogenesis; Rap1; VE-cadherin; migration; adhesion; endothelial cells
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MDPI and ACS Style

Gaonac’h-Lovejoy, V.; Boscher, C.; Delisle, C.; Gratton, J.-P. Rap1 is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting. Cells 2020, 9, 155.

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