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PTEN mediates Notch-dependent stalk cell arrest in angiogenesis

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Item Type:Article
Title:PTEN mediates Notch-dependent stalk cell arrest in angiogenesis
Creators Name:Serra, H. and Chivite, I. and Angulo-Urarte, A. and Soler, A. and Sutherland, J.D. and Arruabarrena-Aristorena, A. and Ragab, A. and Lim, R. and Malumbres, M. and Fruttiger, M. and Potente, M. and Serrano, M. and Fabra, A. and Vinals, F. and Casanovas, O. and Pandolfi, P.P. and Bigas, A. and Carracedo, A. and Gerhardt, H. and Graupera, M.
Abstract:Coordinated activity of VEGF and Notch signals guides the endothelial cell (EC) specification into tip and stalk cells during angiogenesis. Notch activation in stalk cells leads to proliferation arrest via an unknown mechanism. By using gain- and loss-of-function gene-targeting approaches, here we show that PTEN is crucial for blocking stalk cell proliferation downstream of Notch, and this is critical for mouse vessel development. Endothelial deletion of PTEN results in vascular hyperplasia due to a failure to mediate Notch-induced proliferation arrest. Conversely, overexpression of PTEN reduces vascular density and abrogates the increase in EC proliferation induced by Notch blockade. PTEN is a lipid/protein phosphatase that also has nuclear phosphatase-independent functions. We show that both the catalytic and non-catalytic APC/C-Fzr1/Cdh1-mediated activities of PTEN are required for stalk cells' proliferative arrest. These findings define a Notch-PTEN signalling axis as an orchestrator of vessel density and implicate the PTEN-APC/C-Fzr1/Cdh1 hub in angiogenesis.
Keywords:Anaphase-Promoting Complex-Cyclosome, Cdh1 Proteins, Cell Proliferation, Endothelial Cells, Fluorescent Antibody Technique, Immunoblotting, Messenger RNA, Notch Receptors, Physiologic Neovascularization, PTEN Phosphohydrolase, Polymerase Chain Reaction, Animals, Mice
Source:Nature Communications
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Volume:6
Page Range:7935
Date:31 July 2015
Official Publication:https://doi.org/10.1038/ncomms8935
PubMed:View item in PubMed

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