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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716312384 |
| _version_ | 1818285115390820352 |
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| author | Pirjo Spuul Thomas Daubon Bettina Pitter Florian Alonso Isabelle Fremaux IJsbrand Kramer Eloi Montanez Elisabeth Génot |
| author_facet | Pirjo Spuul Thomas Daubon Bettina Pitter Florian Alonso Isabelle Fremaux IJsbrand Kramer Eloi Montanez Elisabeth Génot |
| author_sort | Pirjo Spuul |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T01:03:34Z |
| format | Article |
| id | doaj.art-3c8b887005fb452c8eeef6d1b8944bdd |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T01:03:34Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-3c8b887005fb452c8eeef6d1b8944bdd2022-12-22T00:04:37ZengElsevierCell Reports2211-12472016-10-0117248450010.1016/j.celrep.2016.09.016VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting AngiogenesisPirjo Spuul0Thomas Daubon1Bettina Pitter2Florian Alonso3Isabelle Fremaux4IJsbrand Kramer5Eloi Montanez6Elisabeth Génot7Departement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceDepartement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceWalter-Brendel Center of Experimental Medicine, Ludwig-Maximilians University, Marchioninistrasse 27, 81377 Munich, GermanyDepartement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceDepartement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceDepartement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceWalter-Brendel Center of Experimental Medicine, Ludwig-Maximilians University, Marchioninistrasse 27, 81377 Munich, GermanyDepartement Sciences du Vivant et de la Santé, Université de Bordeaux, 146 rue Léo Saignat, 33000 Bordeaux, FranceDuring 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.http://www.sciencedirect.com/science/article/pii/S2211124716312384cytoskeletonactinVEGF-ANotch/Dll4 signalingpodosomestip cellsangiogenesisretinabasement membranecollagen-IV |
| spellingShingle | Pirjo Spuul Thomas Daubon Bettina Pitter Florian Alonso Isabelle Fremaux IJsbrand Kramer Eloi Montanez Elisabeth Génot VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis Cell Reports cytoskeleton actin VEGF-A Notch/Dll4 signaling podosomes tip cells angiogenesis retina basement membrane collagen-IV |
| title | 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_short | 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 |
| topic | cytoskeleton actin VEGF-A Notch/Dll4 signaling podosomes tip cells angiogenesis retina basement membrane collagen-IV |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716312384 |
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