Figure 10.

Model for dynamin-dependent Rac localization. (A) Rac has been localized to an ARF-6-dependent endosomal-plasma membrane recycling pathway (Radhakrishna et al., 1999). In migrating and spreading cells, integrins control binding sites for active Rac at the plasma membrane to induce lamellipodia and membrane ruffles (Del Pozo et al., 2002). Peripheral ruffles move centripetally and give rise to macropinosomes. Rac is internalized with macropinosomes in a dynamin-dependent manner as a prerequisite for its deactivation and recycling. (B) Dominant-negative dynamin^-2 (DN Dyn2) inhibits Rac internalization leading to segregation of activated Rac into aberrant dorsal membrane ruffles. Subsequently, the Rac recycling pathway is depleted and lamellipodia formation subsides.