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microtubule disruption, with those retaining their ability to migrate in the
absence of functional microtubules, revealed one clear distinction between
them: these cell types differ in their mode of the attachment to the ECM. More
precisely, we must consider different types of integrin-mediated matrix
adhesions. Even under simplified conditions of monolayer culture, at least
four types of structures linking the ECM with the actin cytoskeleton via
transmembrane integrin molecules have been described: ubiquitous 'classical'
focal adhesions (or focal contacts) and focal complexes, and more specialized
fibrillar adhesions, and podosomes (Geiger et al., 2001). In three-dimensional
matrices derived from tissues or cell culture, additional variants of integrin
adhesions appear (Cukierman et al., 2001). Besides morphological distinc-
tions, different classes of integrin-mediated matrix adhesions vary in their
dynamics, protein composition and adhesion strength (Adams, 2001; Geiger et
al., 2001; Wehrle-Haller and Imhof, 2002). Focal complexes begin initially as
dot-like adhesions (less than 1 mm in size) originating at the tips of
lamellipodia or filopodia. They are short-lived structures and either disappear,
or develop into classical focal adhesions (Figure 5.2), elongated oval plaques
several micrometers in size associated with the bundles of actin filaments
('stress fibres'). Fibrillar adhesions evolve from focal adhesions and
participate in the assembly of extracellular fibronectin fibres, while podosomes
are small (0.5 mm) ring-shaped adhesion structures found in specialized cell
types, such as macrophages and osteoclasts (Geiger et al., 2001).
The dependence on microtubules for the locomotion of a particular cell type
correlates with the presence of classical focal adhesions. Cells that form focal
complex type adhesions but do not convert them into focal adhesions can
move successfully without microtubules. These microtubule-independent cell
types include the fish keratocytes mentioned above (Euteneuer and Schliwa,
1984), 'professional' migrating cells such as polymorphonuclear leukocytes
(which actually move even faster after microtubule disruption (Keller and
Niggli, 1993)), and perhaps some poorly adherent cancer cells (Ivanova et al.,
1980; Sroka et al., 2002). Detailed studies of fish keratocytes, for example,
revealed mainly punctate adhesions with an area of less than 1 mm 2 (Lee and
Jacobson, 1997); very few of these adhesions transform into typical focal
adhesions (Anderson and Cross, 2000). In contrast, cell types that require
microtubules for migration are well-attached cells that in addition to focal
complexes demonstrate typical focal adhesions. Microtubule-dependence of
migration was observed in fibroblasts and fibroblast-like cells (Gail and
Boone, 1971; Goldman, 1971; Vasiliev et al., 1970), which move relatively
slowly, but also in fast migrating cells, such as Melb-a melanoblasts or
melanoma B16 cells (Ballestrem et al., 2000). Disruption of microtubules in
such cell types leads to a further increase in the number and size of the focal
adhesions (Bershadsky et al., 1996; Kirchner et al., 2003), which impedes cell
migration by increasing their adhesion to the substrate to the level
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