Biology Reference
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towards antigen-presenting cells possibly to direct lymphokine secretion
(Stowers et al., 1995). Similarly, two groups have now shown independently
that, in a wound-edge model system, the orientation of the centrosome
towards the leading edge of migrating cells also depends on Cdc42 function, as
well as the minus-end-directed microtubule-based motor, cytoplasmic dynein.
In astrocytes, interactions of integrins with the extracellular matrix at the
protruding cell edge lead to polarized recruitment and activation of Cdc42 and
an atypical protein kinase C, which in turn might locally activate cytoplasmic
dynein (Etienne-Manneville and Hall, 2001). Such localized dynein activity at
the cortex in the leading part of the cell could then pull the centrosome
forward (Figure 13.3a). In fibroblasts, centrosome reorientation appears to
precede protrusion formation. It is solely dependent on Cdc42 function and is
Figure 13.3 Potential mechanisms for how Rho proteins could regulate organization and
dynamics of the microtubule cytoskeleton. (a) Cdc42 activity is required for the
reorientation of the centrosome towards the direction of migration, which could occur
through cortical cytoplasmic dynein activity. (b) Stable, detyrosinated microtubules are
induced by RhoA and its downstream effector mDia. (c) RhoA might also cause the
phosphorylation of microtubule-associated proteins and thus destabilize microtubules.
(d) Rac1 and Cdc42 might decrease the microtubule catastrophe frequency and thus
promote microtubule growth through Pak1-dependent phosphorylation of Op18/stathmin.
(e) The regulation of microtubule-plus-end-tracking proteins downstream of Rho GTPases
might also contribute to increased microtubule growth at the cells leading edge.
Microtubules also target focal adhesions and depolymerizing microtubule ends are
created in the cell body by retrograde-flow-induced breakage. The open arrow indicates the
direction of cell migration. Thick black lines represent microtubules and plus and minus
signs indicate microtubule polarity. (A colour reproduction of this figure can be found in
the colour plate section)
