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 hypomorphicC3G allele. C3Ggt/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-β1-positive cell adhesions. In contrast, integrin-β3-positive cell adhesions formed normally. These results show that C3G is required for (1) vascular myogenesis,(2) the formation of paxillin- and integrin β1-positive, but not integrinβ3-positive, cell adhesions and (3) normal response to PDGF, necessary for vascular myogenesis.