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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Autores principales:	Juliete A. F. Silva, Xiaoping Qi, Maria B. Grant, Michael E. Boulton
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f3ea6127e70d498caa8a43211a8d9824
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spelling	oai:doaj.org-article:f3ea6127e70d498caa8a43211a8d98242021-12-02T15:29:03ZSpatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells10.1038/s41598-021-96964-72045-2322https://doaj.org/article/f3ea6127e70d498caa8a43211a8d98242021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96964-7https://doaj.org/toc/2045-2322Abstract 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.Juliete A. F. SilvaXiaoping QiMaria B. GrantMichael E. BoultonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
author	Juliete A. F. Silva Xiaoping Qi Maria B. Grant Michael E. Boulton
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 Portfolio
publishDate	2021
url	https://doaj.org/article/f3ea6127e70d498caa8a43211a8d9824
work_keys_str_mv	AT julieteafsilva spatialandtemporalvegfreceptorintracellulartraffickinginmicrovascularandmacrovascularendothelialcells AT xiaopingqi spatialandtemporalvegfreceptorintracellulartraffickinginmicrovascularandmacrovascularendothelialcells AT mariabgrant spatialandtemporalvegfreceptorintracellulartraffickinginmicrovascularandmacrovascularendothelialcells AT michaeleboulton spatialandtemporalvegfreceptorintracellulartraffickinginmicrovascularandmacrovascularendothelialcells
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Spatial and temporal VEGF receptor intracellular trafficking in microvascular and macrovascular endothelial cells

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