Article (Scientific journals)
PP2A regulatory subunit Balpha controls endothelial contractility and vessel lumen integrity via regulation of HDAC7.
Martin, Maud; Geudens, Ilse; Bruyr, Jonathan et al.
2013In EMBO Journal
Peer Reviewed verified by ORBi
 

Files


Full Text
(186) MARTIN EMBO J 2013.pdf
Publisher postprint (2.88 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
Angiogenesis; cytoskeleton; HDAC; Lumen maintenance; phosphatase
Abstract :
[en] 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 Balpha regulatory subunit of protein phosphatase 2A (PP2A). Deficiency of Balpha in zebrafish precludes vascular lumen stabilization resulting in perfusion defects. Similarly, inactivation of PP2A-Balpha 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-Balpha controls the activity of HDAC7, an essential transcriptional regulator of vascular stability. In the absence of PP2A-Balpha, 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-Balpha/HDAC7/ArgBP2 axis maintains vascular lumens by balancing endothelial cytoskeletal dynamics and cell-matrix adhesion.
Research center :
Giga-Cancer - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Martin, Maud ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Geudens, Ilse
Bruyr, Jonathan
Potente, Michael
Bleuart, Anouk
Lebrun, Marielle  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Simonis, Nicolas
Deroanne, Christophe ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Twizere, Jean-Claude  ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Soubeyran, Philippe
Peixoto, Paul ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Janssens, Veerle
Hofmann, Wolf-Karsten
Claes, Filip
Carmeliet, Peter
Kettmann, Richard ;  Université de Liège - ULiège > Chimie et bio-industries > Biologie cell. et moléc.
Gerhardt, Holger
Dequiedt, Franck  ;  Université de Liège - ULiège > GIGA-Research
More authors (9 more) Less
Language :
English
Title :
PP2A regulatory subunit Balpha controls endothelial contractility and vessel lumen integrity via regulation of HDAC7.
Publication date :
2013
Journal title :
EMBO Journal
ISSN :
0261-4189
eISSN :
1460-2075
Publisher :
Oxford University Press, Oxford, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Interuniversity Attraction Poles Program (IUP-BELSPO PVI/28 and PVII/13)
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
since 06 September 2013

Statistics


Number of views
105 (25 by ULiège)
Number of downloads
1 (1 by ULiège)

Scopus citations®
 
36
Scopus citations®
without self-citations
27
OpenCitations
 
31

Bibliography


Similar publications



Contact ORBi