RRC ID 4779
Author Ohba Y, Ikuta K, Ogura A, Matsuda J, Mochizuki N, Nagashima K, Kurokawa K, Mayer BJ, Maki K, Miyazaki J, Matsuda M.
Title Requirement for C3G-dependent Rap1 activation for cell adhesion and embryogenesis.
Journal EMBO J
Abstract C3G is a guanine nucleotide exchange factor (GEF) for Rap1, and is activated via Crk adaptor protein. To understand the physiological role of C3G, we generated C3G knockout mice. C3G(-/-) homozygous mice died before embryonic day 7.5. The lethality was rescued by the expression of the human C3G transgene, which could be excised upon the expression of Cre recombinase. From the embryo of this mouse, we prepared fibroblast cell lines, MEF-hC3G. Expression of Cre abolished the expression of C3G in MEF-hC3G and inhibited cell adhesion-induced activation of Rap1. The Cre-expressing MEF-hC3G showed impaired cell adhesion, delayed cell spreading and accelerated cell migration. The accelerated cell migration was suppressed by the expression of active Rap1, Rap2 and R-Ras. Expression of Epac and CalDAG-GEFI, GEFs for Rap1, also suppressed the accelerated migration of the C3G-deficient cells. This observation indicated that Rap1 activation was sufficient to complement the C3G deficiency. In conclusion, C3G-dependent activation of Rap1 is required for adhesion and spreading of embryonic fibroblasts and for the early embryogenesis of the mouse.
Volume 20(13)
Pages 3333-41
Published 2001-7-2
DOI 10.1093/emboj/20.13.3333
PMID 11432821
PMC PMC125518
MeSH Animals Cell Adhesion / physiology* Cell Line Cell Membrane / physiology Cell Membrane / ultrastructure Cell Movement / physiology Embryonic and Fetal Development / physiology* Fibroblasts / physiology Gene Deletion Genetic Complementation Test Genotype Guanine Nucleotide-Releasing Factor 2 / deficiency Guanine Nucleotide-Releasing Factor 2 / genetics Guanine Nucleotide-Releasing Factor 2 / metabolism* Guanosine Triphosphate / metabolism Homozygote Humans Integrases / genetics Integrases / metabolism Mice Mice, Knockout Mice, Transgenic Models, Biological Proto-Oncogene Proteins p21(ras) / genetics Proto-Oncogene Proteins p21(ras) / metabolism Viral Proteins* rap GTP-Binding Proteins / genetics rap GTP-Binding Proteins / metabolism rap1 GTP-Binding Proteins / metabolism*
IF 9.889
Times Cited 153
DNA material AxCANCre (RDB01748)