In migrating adherent cells such as fibroblasts and endothelial cells, the 
microtubule-organizing center (MTOC) reorients toward the leading edge [1-3]. 
MTOC reorientation repositions the Golgi toward the front of the cell [1] and 
contributes to directional migration [4]. The mechanism of MTOC reorientation 
and its relation to the formation of stabilized microtubules (MTs) in the 
leading edge, which occurs concomitantly with MTOC reorientation [3], is 
unknown. We show that serum and the serum lipid, lysophosphatidic acid (LPA), 
increased Cdc42 GTP levels and triggered MTOC reorientation in serum-starved 
wounded monolayers of 3T3 fibroblasts. Cdc42, but not Rho or Rac, was both 
sufficient and necessary for LPA-stimulated MTOC reorientation. MTOC 
reorientation was independent of Cdc42-induced changes in actin and was not 
blocked by cytochalasin D. Inhibition of dynein or dynactin blocked LPA- and 
Cdc42-stimulated MTOC reorientation. LPA also stimulates a Rho/mDia pathway that 
selectively stabilizes MTs in the leading edge [5, 6]; however, activators and 
inhibitors of MTOC reorientation and MT stabilization showed that each response 
was regulated independently. These results establish an LPA/Cdc42 signaling 
pathway that regulates MTOC reorientation in a dynein-dependent manner. MTOC 
reorientation and MT stabilization both act to polarize the MT array in 
migrating cells, yet these processes act independently and are regulated by 
separate Rho family GTPase-signaling pathways.