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cooperation between the actin and microtubule system is provided by the
process of assembly, maturation and disassembly of matrix adhesions,
molecular complexes connecting ECM with the actin cytoskeleton via
transmembrane integrin receptors (Geiger et al., 2001; Small et al., 2002).
The interplay between the actin cytoskeleton, microtubule system and
integrin-mediated matrix adhesions is the main subject of the present review.
Coordination of the functions of the actin and microtubule systems is
achieved via a variety of cross-talk mechanisms operating at several levels.
There are, for example, several types of cross-linker proteins, which appear
directly to connect microtubules and actin filaments (Fuchs and Karakesi-
soglou, 2001). However, coordination of the fibre dynamics in time and space
requires more sophisticated regulation than simply direct physical linkage.
The Rho family GTPases were recently shown to control dynamics and
organization not only of the actin cytoskeleton but also of microtubules
(Cook et al., 1998; Daub et al., 2001; Fukata et al., 2002; Ishizaki et al., 2001;
Nakano et al., 2002; Palazzo et al., 2001). One of the mechanisms underlying
such parallel regulation is based on the unique features of a direct Rho target,
Diaphanous related formin homology protein, mDia1 (Alberts, 2002). In the
coming pages, we will discuss the activities of this formin and its possible role
in the coordination of microtubules and the actin cytoskeleton in the course of
focal adhesion remodelling.
Actin, microtubules and cell-matrix adhesions in crawling cell
Crawling locomotion of cells can be viewed as a periodically repeating
sequence of events that includes: formation of pseudopodial protrusions, their
attachment and translocation of the cell body in the direction of the new
attachment sites (Lauffenburger and Horwitz, 1996). All these events can, in
principle, be served by the actin cytoskeleton, in the absence of microtubules.
In particular, formation of filopodial and lamellipodial protrusions is based
exclusively on the regulated polymerization of actin filament superstructures
(Borisy and Svitkina, 2000). Moreover, fragments of fish epidermal
keratocytes, which lack nuclei, centrosomes and microtubules can nevertheless
move with remarkable speed and persistence (Euteneuer and Schliwa, 1984;
Verkhovsky et al., 1999). However, beginning with the pioneering work of
Vasiliev (Vasiliev et al., 1970) it has been shown that, in practice, a majority of
cell types do require the microtubule system for directional locomotion.
Many studies have been performed, using specific microtubule-disrupting
drugs (Peterson and Mitchison, 2002), to elucidate the role of microtubules in
cell migration. Comparisons of cell types, whose migration is sensitive to
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