Signal transduction pathways involved in the regulation of the actin cytoskeleton. (A) The formation of actin-dependent structures, such as stress fibers, focal adhesions, lamellipodia, and filopodia is controlled by cell surface molecules ranging from E-cadherin and integrins to receptors for small components (e.g. TNF-α or LPA) allowing the transmission of extracellular stimuli to the actin cytoskeleton. The Rho GTPases RhoA, Rac1, and Cdc42 are key elements in the regulation of actin filaments. Rac1 and Cdc42 induce actin polymerization through WASP/WAVE family members and WIPs stimulating the Arp2/3 complex. RhoA regulates Dia1/profilin and the ROCK/MLC pathways to promote polymerization of F-actin. (B) Focal adhesions are important structures in linking the ECM to the intracellular actin cytoskeleton via α and β integrin heterodimers. The extracellular part of integrins binds to proteins of the ECM, while the intracellular domain recruits a wide range of intracellular signaling (FAK, Src, etc.) and adaptor proteins (talin, paxillin, vinculin, or p130CAS, etc.) to connect the actin cytoskeleton.