VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis

During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling...

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Detalles Bibliográficos
Autores: Spuul, Pirjo, Daubon, Thomas, Pitter, Bettina, Alonso, Florian, Fremaux, Isabelle, Kramer, Ijsbrand, Montañez, Eloi, Génot, Elisabeth
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/155801
Acceso en línea:https://hdl.handle.net/2445/155801
Access Level:acceso abierto
Palabra clave:Col·lagen
Genètica
Metabolisme
Factor de creixement de l'endoteli vascular
Collagen
Genetics
Metabolism
Vascular endothelial growth factors
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spelling VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesisSpuul, PirjoDaubon, ThomasPitter, BettinaAlonso, FlorianFremaux, IsabelleKramer, IjsbrandMontañez, EloiGénot, ElisabethCol·lagenGenèticaMetabolismeFactor de creixement de l'endoteli vascularCollagenGeneticsMetabolismVascular endothelial growth factorsDuring angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.Elsevier2020202020162020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion17 p.application/pdfhttps://hdl.handle.net/2445/155801Articles publicats en revistes (Ciències Fisiològiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1016/j.celrep.2016.09.016Cell Reports, 2016, vol. 17, num. 2, p. 484-500https://doi.org/10.1016/j.celrep.2016.09.016cc-by (c) Spuul, Pirjo et al., 2016http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1558012026-05-29T05:05:01Z
dc.title.none.fl_str_mv VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
title VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
spellingShingle VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
Spuul, Pirjo
Col·lagen
Genètica
Metabolisme
Factor de creixement de l'endoteli vascular
Collagen
Genetics
Metabolism
Vascular endothelial growth factors
title_short VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
title_full VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
title_fullStr VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
title_full_unstemmed VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
title_sort VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
dc.creator.none.fl_str_mv Spuul, Pirjo
Daubon, Thomas
Pitter, Bettina
Alonso, Florian
Fremaux, Isabelle
Kramer, Ijsbrand
Montañez, Eloi
Génot, Elisabeth
author Spuul, Pirjo
author_facet Spuul, Pirjo
Daubon, Thomas
Pitter, Bettina
Alonso, Florian
Fremaux, Isabelle
Kramer, Ijsbrand
Montañez, Eloi
Génot, Elisabeth
author_role author
author2 Daubon, Thomas
Pitter, Bettina
Alonso, Florian
Fremaux, Isabelle
Kramer, Ijsbrand
Montañez, Eloi
Génot, Elisabeth
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Col·lagen
Genètica
Metabolisme
Factor de creixement de l'endoteli vascular
Collagen
Genetics
Metabolism
Vascular endothelial growth factors
topic Col·lagen
Genètica
Metabolisme
Factor de creixement de l'endoteli vascular
Collagen
Genetics
Metabolism
Vascular endothelial growth factors
description During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells. Using a retinal neovascularization model, we demonstrate that tip cells assemble podosomes during physiological angiogenesis in vivo. In the retina, podosomes are also part of an interconnected network that surrounds large microvessels and impinges on the underlying basement membrane. Consistently, collagen-IV is scarce in podosome areas. Moreover, Notch inhibition exacerbates podosome formation and collagen-IV loss. We propose that the localized proteolytic action of podosomes on basement membrane collagen-IV facilitates endothelial cell sprouting and anastomosis within the developing vasculature. The identification of podosomes as key components of the sprouting machinery provides another opportunity to target angiogenesis therapeutically.
publishDate 2016
dc.date.none.fl_str_mv 2016
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/155801
url https://hdl.handle.net/2445/155801
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1016/j.celrep.2016.09.016
Cell Reports, 2016, vol. 17, num. 2, p. 484-500
https://doi.org/10.1016/j.celrep.2016.09.016
dc.rights.none.fl_str_mv cc-by (c) Spuul, Pirjo et al., 2016
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Spuul, Pirjo et al., 2016
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 17 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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