NRP2 as an emerging angiogenic player; promoting endothelial cell adhesion and migration by regulating recycling of α5 integrin

Alghamdi, Abdullah, Benwell, Christopher, Atkinson, Samuel, Lambert, Jordi, Johnson, Robert and Robinson, Stephen (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

[img]
Preview
PDF (Published_Version) - Published Version
Available under License Creative Commons Attribution.

Download (4MB) | Preview

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
Related URLs:
Depositing User: LivePure Connector
Date Deposited: 20 May 2020 00:14
Last Modified: 01 Sep 2020 23:55
URI: https://ueaeprints.uea.ac.uk/id/eprint/75250
DOI: 10.3389/fcell.2020.00395

Actions (login required)

View Item View Item