NRP2 as an Emerging Angiogenic Player; Promoting Endothelial Cell Adhesion and Migration by Regulating Recycling of α5 Integrin.

Frontiers in Cell and Developmental Biology
Abdullah A A AlghamdiStephen D Robinson

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 organization. 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 pla...Continue Reading

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Citations

Jul 28, 2020·International Journal of Molecular Sciences·Jennifer L HarmanCaroline Pellet-Many
Aug 9, 2020·Frontiers in Cell and Developmental Biology·Aurore Dumond, Gilles Pagès
Apr 13, 2021·Brain, Behavior, & Immunity Health·Francisco J Barrantes
Jan 15, 2022·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shuai LuoJunjie Zhang

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Methods Mentioned

BETA
transgenic
PCR
GTPase
GTPases
co-immunoprecipitation
coimmunoprecipitation
immunoprecipitation
magnetic
transfection
electrophoresis

Software Mentioned

Image J TM MTrackJ
Mesna
ImageJ
GraphPad Prism
MaxQuant
mTrackJ

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