Please use this identifier to cite or link to this item:
Title: VEGF-A/Notch-induced podosomes proteolyse basement membrane collagen-IV during retinal sprouting angiogenesis
Author: Spuul, Pirjo
Daubon, Thomas
Pitter, Bettina
Alonso, Florian
Fremaux, Isabelle
Kramer, Ijsbrand
Montañez, Eloi
Génot, Elisabeth
Keywords: Col·lagen
Factor de creixement de l'endoteli vascular
Vascular endothelial growth factors
Issue Date: 4-Oct-2016
Publisher: Elsevier
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Cell Reports, 2016, vol. 17, num. 2, p. 484-500
Related resource:
ISSN: 2211-1247
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

Files in This Item:
File Description SizeFormat 
697774.pdf8.83 MBAdobe PDFView/Open

This item is licensed under a Creative Commons License Creative Commons