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PP2A regulatory subunit Bα controls endothelial contractility and vessel lumen integrity via regulation of HDAC7
Author(s) -
Martin Maud,
Geudens Ilse,
Bruyr Jonathan,
Potente Michael,
Bleuart Anouk,
Lebrun Marielle,
Simonis Nicolas,
Deroanne Christophe,
Twizere JeanClaude,
Soubeyran Philippe,
Peixoto Paul,
Mottet Denis,
Janssens Veerle,
Hofmann WolfKarsten,
Claes Filip,
Carmeliet Peter,
Kettmann Richard,
Gerhardt Holger,
Dequiedt Franck
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.187
Subject(s) - biology , protein phosphatase 2 , contractility , protein subunit , microbiology and biotechnology , phosphorylation , endocrinology , phosphatase , biochemistry , gene
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.