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Requirement for C3G‐dependent Rap1 activation for cell adhesion and embryogenesis
Author(s) -
Ohba Yusuke,
Ikuta Koichi,
Ogura Atsuo,
Matsuda Junichiro,
Mochizuki Naoki,
Nagashima Kazuo,
Kurokawa Kazuo,
Mayer Bruce J.,
Maki Kazushige,
Miyazaki Junichi,
Matsuda Michiyuki
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.13.3333
Subject(s) - library science , biology , art history , history , computer science
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.