Fig. 3. Potential mechanisms for how asymmetries of the microtubule cytoskeleton might establish cell polarization. (a) Targeting of focal adhesions in the rear of the cell and kinesin-dependent transport of a focal-adhesion-dissociation factor to the adhesion sites might induce the retraction of the cell tail. (b-f) Microtubules might modulate the activity of Rho GTPases by a number of hypothetical mechanisms: (b) the activity of GEFs could be regulated simply by their association with the microtubule cytoskeleton; (c) in the case of RhoA, GEFs such as p190RhoGEF could be activated by their release from depolymerising microtubules in the cell body; (d) the local activation of a RhoG-specific GEF, TrioGEF1, and thus RhoG, a Rho protein upstream of Rac1 and Cdc42Hs, appears to be dependent on some sort of kinesin-mediated transport process; (e) association with the microtubule-plus-end-binding protein APC that is enriched in the lamellipodium could locally activate Rac1-specific GEFs such as Asef; (f) finally, microtubule-dependent regulation of phosphoinositide 3-kinase could activate Rac1 through PtdIns(3,4,5)P₃-binding GEFs such as Vav.