Platelet-derived growth factor receptor-alpha is a key determinant of smooth muscle alpha-actin filaments in bone marrow-derived mesenchymal stem cells.
Smooth muscle alpha-actin filaments are a defining feature of mesenchymal stem cells, and of mesenchyme-derived contractile smooth muscle cells, pericytes and myofibroblasts. Here, we show that adult bone marrow-derived mesenchymal stem cells express abundant cell surface platelet-derived growth factor receptor-alpha, having a high ratio to platelet-derived growth factor receptor-beta. Signaling through platelet-derived growth factor receptor-alpha increases smooth muscle alpha-actin filaments by activating RhoA, which results in Rho-associated kinase (ROCK)-dependent cofilin phosphorylation, enhancing smooth muscle alpha-actin filament polymerization, and also upregulates smooth muscle alpha-actin expression. In contrast, platelet-derived growth factor receptor-beta signaling strongly upregulates RhoE, which inhibits ROCK activity, promoting smooth muscle alpha-actin filament depolymerization. This study thus provides new insights into the distinct roles of platelet-derived growth factor receptor-alpha and -beta signaling in regulating the adult mesenchymal stem cell contractile cytoskeleton.
Ball
Stephen G
SG
UK Centre for Tissue Engineering, Faculty of Life Sciences, The University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
Shuttleworth
C Adrian
CA
Kielty
Cay M
CM
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells / Q000737:chemistry*; D003331:Coronary Vessels / Q000166:cytology; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000737:chemistry*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D051339:Actin Depolymerizing Factors; D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D011108:Polymers; C066737:RHOA protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein