Mol Cell Biol, August 1998, p. 4761-4771, Vol. 18, No. 8
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
The Ludwig Institute for Cancer Research,
Received 29 December 1997/Returned for modification 5 February
1998/Accepted 3 May 1998
The actin cytoskeleton is regulated by Rho family proteins: in
fibroblasts, Rho mediates the formation of actin stress fibers, whereas
Rac regulates lamellipodium formation and Cdc42 controls filopodium
formation. We have cloned the mouse RhoE gene, whose product is a member of the Rho family that shares (except in one amino
acid) the conserved effector domain of RhoA, RhoB, and RhoC. RhoE is
able to bind GTP but does not detectably bind GDP and has low intrinsic
GTPase activity compared with Rac. The role of RhoE in regulating actin
organization was investigated by microinjection in Bac1.2F5 macrophages
and MDCK cells. In macrophages, RhoE induced actin reorganization,
leading to the formation of extensions resembling filopodia and
pseudopodia. In MDCK cells, RhoE induced the complete disappearance of
stress fibers, together with cell spreading. However, RhoE did not
detectably affect the actin bundles that run parallel to the outer
membranes of cells at the periphery of colonies, which are known to be
dependent on RhoA. In addition, RhoE induced an increase in the speed
of migration of hepatocyte growth factor/scatter factor-stimulated MDCK
cells, in contrast to the previously reported inhibition produced by
activated RhoA. The subcellular localization of RhoE at the lateral
membranes of MDCK cells suggests a role in cell-cell adhesion, as has
been shown for RhoA. These results suggest that RhoE may act to inhibit signalling downstream of RhoA, altering some RhoA-regulated responses, such as stress fiber formation, but not affecting others, such as
peripheral actin bundle formation.
*
Corresponding author. Mailing address: The Ludwig
Institute for Cancer Research, 91 Riding House St., London W1P 8BT,
United Kingdom. Phone: (44)-171-878-4088. Fax: (44)-171-878-4040.
E-mail: anne{at}ludwig.ucl.ac.uk.
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