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Figure 5.2 Focal adhesion as a mechanosensor. The focal adhesion is a multi-molecular
complex connecting the extracellular matrix with the actin cytoskeleton. Heterodimeric
transmembrane integrin receptors bind matrix proteins via their extracellular domains,
while their cytoplasmic domains are associated with a dense submembrane plaque
containing more than 50 different proteins ('boxes' enclosed in the oval area), including
structural elements, as well as proteins involved in signal transduction. The plaque, in turn,
is connected to the termini of actin filament bundles. The assembly and maintenance of
focal adhesions depend on local mechanical forces. This force may be generated by myosin
II-driven isometric contraction of the actin cytoskeleton, or by extracellular perturbations
such as matrix stretching or fluid shear stress. Force-induced assembly of the adhesion
plaque leads to the activation of a variety of signalling pathways that control cell
proliferation, differentiation and survival (e.g. MAP kinase and PI 3-kinase pathways) as
well as the organization of the cytoskeleton (e.g. Rho family GTPase pathways). Rho, in
particular, is an indispensable regulator of focal adhesion assembly affecting actin
polymerization and myosin II driven contractility. Reproduced with permission from
Geiger and Bershadsky (2002)
incompatible with locomotion (Ballestrem et al., 2000). Thus, the requirement
for microtubules in cell migration depends on the mode of formation of
integrin-dependent cell-matrix contacts, and applies mainly to cells that form
classical focal adhesions.
A second important fact, which sheds light on the role of microtubules in
cell locomotion, is their involvement in the regulation of myosin II-driven
contractility. Since the studies of Danowski (1989), it has become increasingly
clear that microtubule systems share the ability to suppress cell contractility.
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