The guanine nucleotide exchange factor C3G is necessary for the formation of focal adhesions and vascular maturation

Development. 2003 Jan;130(2):355-67. doi: 10.1242/dev.00217.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Blood Vessels / embryology*
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Cytoskeletal Proteins / metabolism
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / pathology
  • Embryo, Mammalian / physiology
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Focal Adhesions / physiology*
  • Gene Expression
  • Guanine Nucleotide-Releasing Factor 2 / genetics
  • Guanine Nucleotide-Releasing Factor 2 / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Integrin beta1 / metabolism
  • Integrin beta3 / metabolism
  • Laminin / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mutation
  • Paxillin
  • Phenotype
  • Phosphoproteins / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Platelet-Derived Growth Factor / metabolism
  • Signal Transduction / physiology
  • Vinculin / metabolism
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Actins
  • Cytoskeletal Proteins
  • Fibronectins
  • Guanine Nucleotide-Releasing Factor 2
  • Integrin beta1
  • Integrin beta3
  • Laminin
  • Membrane Glycoproteins
  • Paxillin
  • Phosphoproteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Platelet-Derived Growth Factor
  • Pxn protein, mouse
  • nidogen
  • ras GTPase-Activating Proteins
  • Vinculin