Ephrin-A5 induces collapse of growth cones by activating Rho and Rho kinase

The ephrins, ligands of Eph receptor tyrosine kinases, have been shown to a ct as repulsive guidance molecules and to induce collapse of neuronal growt h cones. For the first time, we show that the ephrin-A5 collapse is mediate d by activation of the small GTPase Rho and its downstream effector Rho kin ase, In ephrin-A5-treated retinal ganglion cell cultures, Rho was activated and Rac was downregulated. Pretreatment of ganglion cell axons with C3-tra nsferase, a specific inhibitor of the Rho GTPase, or with Y-27632, a specif ic inhibitor of the Rho kinase, strongly reduced the collapse rate of retin al growth cones. These results suggest that activation of Rho and its downs tream effector Rho kinase are important elements of the ephrin-A5 signal tr ansduction pathway.