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PP2A regulatory subunit Bα controls endothelial contractility and vessel lumen integrity via regulation of HDAC7

Item Type:Article
Title:PP2A regulatory subunit Bα controls endothelial contractility and vessel lumen integrity via regulation of HDAC7
Creators Name:Martin, M. and Geudens, I. and Bruyr, J. and Potente, M. and Bleuart, A. and Lebrun, M. and Simonis, N. and Deroanne, C. and Twizere, J.C. and Soubeyran, P. and Peixoto, P. and Mottet, D. and Janssens, V. and Hofmann, W.K. and Claes, F. and Carmeliet, P. and Kettmann, R. and Gerhardt, H. and Dequiedt, F.
Abstract:To supply tissues with nutrients and oxygen, the cardiovascular system forms a seamless, hierarchically branched, network of lumenized tubes. Here, we show that maintenance of patent vessel lumens requires the Bα regulatory subunit of protein phosphatase 2A (PP2A). Deficiency of Bα in zebrafish precludes vascular lumen stabilization resulting in perfusion defects. Similarly, inactivation of PP2A-Bα in cultured ECs induces tubulogenesis failure due to alteration of cytoskeleton dynamics, actomyosin contractility and maturation of cell-extracellular matrix (ECM) contacts. Mechanistically, we show that PP2A-Bα controls the activity of HDAC7, an essential transcriptional regulator of vascular stability. In the absence of PP2A-Bα, transcriptional repression by HDAC7 is abrogated leading to enhanced expression of the cytoskeleton adaptor protein ArgBP2. ArgBP2 hyperactivates RhoA causing inadequate rearrangements of the EC actomyosin cytoskeleton. This study unravels the first specific role for a PP2A holoenzyme in development: the PP2A-Bα/HDAC7/ArgBP2 axis maintains vascular lumens by balancing endothelial cytoskeletal dynamics and cell-matrix adhesion.
Keywords:Angiogenesis, Cytoskeleton, HDAC, Lumen Maintenance, Phosphatase, Animals, Zebrafish
Source:EMBO Journal
Publisher:Nature Publishing Group
Page Range:2491-2503
Date:11 September 2013
Official Publication:https://doi.org/10.1038/emboj.2013.187
PubMed:View item in PubMed

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