The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation.
The Ras signalling pathway has major roles in normal cell function and oncogenesis. C3G is a guanine nucleotide exchange factor for members of the Ras family of GTPases. We generated a mouse strain with a hypomorphic C3G allele. C3G(gt/gt) mutant embryos died of vascular defects around E11.5 due to haemorrhage and vascular integrity defects. Vascular supporting cells did not develop appropriately. C3G-deficient fibroblasts responded to PDGF-BB abnormally, exhibited cell adhesion defects and lacked paxillin and integrin-beta1-positive cell adhesions. In contrast, integrin-beta3-positive cell adhesions formed normally. These results show that C3G is required for (1) vascular myogenesis, (2) the formation of paxillin- and integrin beta1-positive, but not integrin beta3-positive, cell adhesions and (3) normal response to PDGF, necessary for vascular myogenesis.
Voss
Anne K
AK
Development and Neurobiology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. avoss@wehi.edu.au
Gruss
Peter
P
Thomas
Tim
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000196:embryology*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D015870:Gene Expression; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019012:Integrin beta1 / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009154:Mutation; D051419:Paxillin; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016596:Vinculin / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
D000199:Actins; D003598:Cytoskeletal Proteins; D005353:Fibronectins; D020735:Guanine Nucleotide-Releasing Factor 2; D019012:Integrin beta1; D039661:Integrin beta3; D007797:Laminin; D008562:Membrane Glycoproteins; D051419:Paxillin; D010750:Phosphoproteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; C496062:Pxn protein, mouse; C029967:nidogen; D020703:ras GTPase-Activating Proteins; D016596:Vinculin