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Abstract
Substrate anchorage and cell locomotion entail the initiation and development of different
classes of contact sites, which are associated with the different compartments of
the actin cytoskeleton. The Rho-family GTPases are implicated in the signalling pathways
that dictate contact initiation, maturation and turnover, but their individual roles
in these processes remain to be defined.
We monitored the dynamics of peripheral, Rac-induced focal complexes in living cells
in response to perturbations of Rac and Rho activity and myosin contractility. We
show that focal complexes formed in response to Rac differentiated into focal contacts
upon upregulation of Rho. Focal complexes were dissociated by inhibitors of myosin-II-dependent
contractility but not by an inhibitor of Rho-kinase. The downregulation of Rac promoted
the enlargement of focal contacts, whereas a block in the Rho pathway not only caused
a dissolution of focal contacts but also stimulated membrane ruffling and formation
of new focal complexes, which were associated with the advance of the cell front.
Rac functions to signal the creation of new substrate contacts at the cell front,
which are associated with the induction of ruffling lamellipodia, whereas Rho serves
in the maturation of existing contacts, with both contact types requiring contractility
for their formation. The transition from a focal complex to a focal contact is associated
with a switch to Rho-kinase dependence. Rac and Rho also influence the development
of focal contacts and focal complexes, respectively, through mutually antagonistic
pathways.