title: The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation.
abstract: 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.
authors.affiliation: Development and Neurobiology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia. avoss@wehi.edu.au
authors.forename: Anne K
authors.initials: AK
authors.lastname: Voss
authors.forename: Peter
authors.initials: P
authors.lastname: Gruss
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
mesh_terms: 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*
chemical_list: 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