Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells
Abstract The vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organel...
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2021-08-01
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Online Access: | https://doi.org/10.1038/s41598-021-96964-7 |
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doaj-f3ea6127e70d498caa8a43211a8d98242021-09-05T11:32:14ZengNature Publishing GroupScientific Reports2045-23222021-08-0111111610.1038/s41598-021-96964-7Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cellsJuliete A. F. Silva0Xiaoping Qi1Maria B. Grant2Michael E. Boulton3Department of Ophthalmology and Visual Sciences, University of Alabama at BirminghamDepartment of Ophthalmology and Visual Sciences, University of Alabama at BirminghamDepartment of Ophthalmology and Visual Sciences, University of Alabama at BirminghamDepartment of Ophthalmology and Visual Sciences, University of Alabama at BirminghamAbstract The vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organelles involved in this process is unclear. This study reports the effect of exogenous VEGF on translocation of VEGFRs and organelles in micro- and macrovascular endothelial cells. We showed that VEGF is responsible for: a rapid and substantial nuclear translocation of VEGFRs; VEGFR1 and VEGFR2 exhibit distinct spatial, temporal and structural translocation characteristics both in vitro and in vivo and this determines the nuclear VEGFR1:VEGFR2 ratio which differs between microvascular and macrovascular cells; VEGFR2 nuclear translocation is associated with the endosomal pathway transporting the receptor from Golgi in microvascular endothelial cells; and an increase in the volume of intracellular organelles. In conclusion, the nuclear translocation of VEGFRs is both receptor and vessel (macro versus micro) dependent and the endosomal pathway plays a key role in the translocation of VEGFRs to the nucleus and the subsequent export to the lysosomal system. Modulating VEGF-mediated VEGFR1 and VEGFR2 intracellular transmigration pathways may offer an alternative for the development of new anti-angiogenic therapies.https://doi.org/10.1038/s41598-021-96964-7 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Juliete A. F. Silva Xiaoping Qi Maria B. Grant Michael E. Boulton |
spellingShingle |
Juliete A. F. Silva Xiaoping Qi Maria B. Grant Michael E. Boulton Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells Scientific Reports |
author_facet |
Juliete A. F. Silva Xiaoping Qi Maria B. Grant Michael E. Boulton |
author_sort |
Juliete A. F. Silva |
title |
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
title_short |
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
title_full |
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
title_fullStr |
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
title_full_unstemmed |
Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
title_sort |
spatial and temporal vegf receptor intracellular trafficking in microvascular and macrovascular endothelial cells |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-08-01 |
description |
Abstract The vascular endothelial growth factor receptors (VEGFRs) can shape the neovascular phenotype of vascular endothelial cells when translocated to the nucleus, however the spatial and temporal changes in the intracellular distribution and translocation of VEGFRs to the nucleus and the organelles involved in this process is unclear. This study reports the effect of exogenous VEGF on translocation of VEGFRs and organelles in micro- and macrovascular endothelial cells. We showed that VEGF is responsible for: a rapid and substantial nuclear translocation of VEGFRs; VEGFR1 and VEGFR2 exhibit distinct spatial, temporal and structural translocation characteristics both in vitro and in vivo and this determines the nuclear VEGFR1:VEGFR2 ratio which differs between microvascular and macrovascular cells; VEGFR2 nuclear translocation is associated with the endosomal pathway transporting the receptor from Golgi in microvascular endothelial cells; and an increase in the volume of intracellular organelles. In conclusion, the nuclear translocation of VEGFRs is both receptor and vessel (macro versus micro) dependent and the endosomal pathway plays a key role in the translocation of VEGFRs to the nucleus and the subsequent export to the lysosomal system. Modulating VEGF-mediated VEGFR1 and VEGFR2 intracellular transmigration pathways may offer an alternative for the development of new anti-angiogenic therapies. |
url |
https://doi.org/10.1038/s41598-021-96964-7 |
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