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Alghamdi, Abdullah, Benwell, Christopher, Atkinson, Samuel, Lambert, Jordi, Johnson, Robert and Robinson, Stephen 
ORCID: https://orcid.org/0000-0002-6606-7588
(2020)
NRP2 as an emerging angiogenic player; promoting endothelial cell adhesion and migration by regulating recycling of α5 integrin.
Frontiers in Cell and Developmental Biology, 8.
ISSN 2296-634X
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Abstract
Angiogenesis relies on the ability of endothelial cells (ECs) to migrate over the extracellular matrix via integrin receptors to respond to an angiogenic stimulus. Of the two neuropilin (NRP) orthologs to be identified, both have been reported to be expressed on normal blood and lymphatic ECs, and to play roles in the formation of blood and lymphatic vascular networks during angiogenesis. Whilst the role of NRP1 and its interactions with integrins during angiogenesis has been widely studied, the role of NRP2 in ECs is poorly understood. Here we demonstrate that NRP2 promotes Rac-1 mediated EC adhesion and migration over fibronectin (FN) matrices in a mechanistically distinct fashion to NRP1, showing no dependence on β3 integrin (ITGB3) expression, or VEGF stimulation. Furthermore, we highlight evidence of a regulatory crosstalk between NRP2 and α5 integrin (ITGA5) in ECs, with NRP2 depletion eliciting an upregulation of ITGA5 expression and disruptions in ITGA5 cellular organisation. Finally, we propose a mechanism whereby NRP2 promotes ITGA5 recycling in ECs; NRP2 depleted ECs were found to exhibit reduced levels of total ITGA5 subunit recycling compared to wild-type (WT) ECs. Our findings expose NRP2 as a novel angiogenic player by promoting ITGA5-mediated EC adhesion and migration on FN.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | neuropilins,cell migration,endothelium,integrins,protein trafficking,developmental biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1309 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Science > School of Pharmacy |
| UEA Research Groups: | Faculty of Science > Research Groups > Cells and Tissues Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 20 May 2020 00:14 |
| Last Modified: | 09 Mar 2024 01:23 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/75250 |
| DOI: | 10.3389/fcell.2020.00395 |
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