1. Cgnl1, an endothelial junction complex protein, regulates GTPase mediated angiogenesis.
- Author
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Chrifi I, Hermkens D, Brandt MM, van Dijk CGM, Bürgisser PE, Haasdijk R, Pei J, van de Kamp EHM, Zhu C, Blonden L, Kros JM, Duncker DJ, Duckers HJ, and Cheng C
- Subjects
- Actin Cytoskeleton metabolism, Animals, Cell Adhesion physiology, Cytoskeletal Proteins genetics, Endothelium, Vascular metabolism, Humans, Intercellular Junctions metabolism, Membrane Proteins genetics, Mice, Inbred C57BL, Adherens Junctions metabolism, Cytoskeletal Proteins metabolism, Endothelial Cells metabolism, GTP Phosphohydrolases metabolism, Membrane Proteins metabolism, Neovascularization, Physiologic physiology
- Abstract
Aims: The formation of cell-cell and cell-extra cellular matrix (ECM) contacts by endothelial cells (ECs) is crucial for the stability and integrity of a vascular network. We previously identified cingulin-like 1 (Cgnl1) in a transcriptomic screen for new angiogenic modulators. Here we aim to study the function of the cell-cell junction associated protein Cgnl1 during vessel formation., Methods and Results: Unlike family member cingulin, Cgnl1 expression is enriched in ECs during vascular growth. Cgnl1 is important for the formation of multicellular tubule structures, as shown in vitro using loss-of function assays in a 3D matrix co-culture system that uses primary human ECs and supporting mural cells. Further studies revealed that Cgnl1 regulates vascular growth by promoting Ve-cadherin association with the actin cytoskeleton, thereby stabilizing adherens junctions. Cgnl1 also regulates focal adhesion assembly in response to ECM contact, promoting vinculin and paxillin recruitment and focal adhesion kinase signalling. In vivo, we demonstrate in a postnatal retinal vascular development model in mice that Cgnl1 function is crucial for sustaining neovascular growth and stability., Conclusions: Our data demonstrate a functional relevance for Cgnl1 as a defining factor in new vessel formation both in vitro and in vivo., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2017
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