Actin-binding proteins control the location, organization, and behavior of actin filaments. The activities of these proteins are, in turn, controlled by extracellular signal molecules, allowing the cell to rearrange its actin cytoskeleton in response to its environment.

These extracellular signals act through a variety of cell-surface receptor proteins, which activate various intracellular signaling pathways. Many of these pathways converge on a group of closely related monomeric GTPases that are part of the Rho protein family. Monomeric GTPases behave as molecular switches that control intracellular processes by cycling between an active GTP-bound state and an inactive GDP-bound state.

In the case of the actin cytoskeleton, different Rho family members alter the organization of actin filaments in different ways. For example, one Rho family member triggers the bundling of actin filaments and activation of the formin proteins that promote the formation of filopodia. Another Rho GTPase might stimulate ARP complexes at the cell’s leading edge, promoting the formation of lamellipodia and membrane ruffling.

Finally, activation of the founding member of the Rho family drives the bundling of actin filaments with myosin motor proteins and the clustering of cellsurface integrins, actions that promote cell crawling.