Regulation of the actin cytoskeleton by PI(4,5)P2 and PI(3,4,5)P3

The actin cytoskeleton is fundamental for various motile and morphogenetic processes in cells. The structure and dynamics of the actin cytoskeleton are regulated by a wide array of actin-binding proteins, whose activities are controlled by various signal transduction pathways. Recent studies have shown that certain membrane phospholipids, especially PI(4,5)P2 and PI(3,4,5)P3, regulate actin filament assembly in cells and in cell extracts. PI(4,5)P2 appears to be a general regulator of actin polymerization at the plasma membrane or at membrane microdomains, whereas PI(3,4,5)P3 promotes the assembly of specialized actin filament structures in response to some growth factors. Biochemical studies have demonstrated that the activities of many proteins promoting actin assembly are upregulated by PI(4,5)P2, whereas proteins that inhibit actin assembly or promote filament disassembly are down-regulated by PI(4,5)P2. PI(3,4,5)P3 promotes its effects on the actin cytoskeleton mainly through activation of the Rho family of small GTPases. In addition to their effects on actin dynamics, both PI(4,5)P2 and PI(3,4,5)P3 promote the formation of specific actin filament structures through activation/inactivation of actin filament cross-linking proteins and proteins that mediate cytoskeleton-plasma membrane interactions.