Biology Reference
In-Depth Information
Figure 5.7 A scheme depicting a possible role of mDia1 in the organization of the
microtubule system. In areas with high mDia1 activity, microtubules slow down their plus-
end dynamics, while their minus-ends, even those not associated with the centrosome, are
protected from depolymerization. This leads to accumulation of microtubules in the
regions with higher mDia1 activity, presumably those regions adjacent to the source of
integrin signalling, e.g., focal adhesions (see text for detailed discussion)
from this area; (3) facilitation of direct microtubule targeting to the focal
adhesion plaques. These effects should make it possible for the cell to orientate
and migrate in the direction determined by the integrin-mediated ECM
signals, which could be either a gradient of ECM molecule concentration
(Brandley and Schnaar, 1989), or gradient of substrate rigidity (Lo et al.,
2000). In particular, accumulation of microtubules behind the focal adhesions
inducing relaxation of contractility should brake the positive feedback loop of
tension-induced focal adhesion growth (see previous section) allowing the cell
to avoid both abrupt focal adhesion breakage, and their indefinite growth
(Figure 5.8). Instead, the older focal adhesions, which have attracted
microtubules and therefore reduced the actomyosin tension in their proximity,
will weaken or disassemble, giving the cell the ability to relocate onto the new
substrate area. Thus, microtubules facilitate directional migration of cells that
are attached to a substrate with well-developed focal adhesions. Rapidly
migrating cells forming mainly small focal complexes are less dependent on
the microtubule-mediated regulation.
Conclusion and perspectives
In this review, we highlighted several pathways coupling formation and
growth of focal adhesions with contractile activity and cytoskeletal dynamics.
Focal adhesions function as mechanosensors, responding to physical forces
