Alpha-parvin controls vascular mural cell recruitment to vessel wall by regulating RhoA/ROCK signalling.
During blood vessel development, vascular smooth muscle cells (vSMCs) and pericytes (PCs) are recruited to nascent vessels to stabilize them and to guide further vessel remodelling. Here, we show that loss of the focal adhesion (FA) protein alpha-parvin (alpha-pv) in mice leads to embryonic lethality due to severe cardiovascular defects. The vascular abnormalities are characterized by poor vessel remodelling, impaired coverage of endothelial tubes with vSMC/PCs and defective association of the recruited vSMC/PCs with endothelial cells (ECs). Alpha-pv-deficient vSMCs are round and hypercontractile leading either to their accumulation in the tissue or to local vessel constrictions. Because of the high contractility, alpha-pv-deficient vSMCs fail to polarize their cytoskeleton resulting in loss of persistent and directed migration. Mechanistically, the absence of alpha-pv leads to increased RhoA and Rho-kinase (ROCK)-mediated signalling, activation of myosin II and actomyosin hypercontraction in vSMCs. Our findings show that alpha-pv represents an essential adhesion checkpoint that controls RhoA/ROCK-mediated contractility in vSMCs.
Montanez
Eloi
E
Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany.
Wickström
Sara A
SA
Altstätter
Johannes
J
Chu
Haiyan
H
Fässler
Reinhard
R
D000818:Animals; D001808:Blood Vessels / Q000166:cytology*; D002318:Cardiovascular Diseases / Q000196:embryology / Q000235:genetics; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D042783:Endothelial Cells / Q000166:cytology; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D020286:Pericytes / Q000166:cytology; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D008840:Microfilament Proteins; C519774:Parva protein, mouse; D034741:RNA, Small Interfering; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein