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J. Cell Biol.,
Volume 144, Number 6, March 22, 1999 1235-1244
MRC Laboratory for Molecular Cell Biology, CRC Oncogene and Signal Transduction Group and Department of
Biochemistry, University College London, London WC1E 6BT, United Kingdom
Cell movement is essential during embryogenesis to establish tissue patterns and to drive morphogenetic pathways and in the adult for tissue repair
and to direct cells to sites of infection. Animal cells
move by crawling and the driving force is derived primarily from the coordinated assembly and disassembly
of actin filaments. The small GTPases, Rho, Rac, and
Cdc42, regulate the organization of actin filaments and
we have analyzed their contributions to the movement
of primary embryo fibroblasts in an in vitro wound healing assay. Rac is essential for the protrusion of
lamellipodia and for forward movement. Cdc42 is required to maintain cell polarity, which includes the
localization of lamellipodial activity to the leading
edge and the reorientation of the Golgi apparatus in
the direction of movement. Rho is required to maintain
cell adhesion during movement, but stress fibers and
focal adhesions are not required. Finally, Ras regulates
focal adhesion and stress fiber turnover and this is essential for cell movement. We conclude that the signal
transduction pathways controlled by the four small GTPases, Rho, Rac, Cdc42, and Ras, cooperate to promote cell movement.
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