Module 4: Figure actin remodelling proteins
Wiskott–Aldrich syndrome protein (WASP) and WASP verprolin homologous (WAVE) proteins orchestrate remodelling of the actin cytoskeleton.
The Wiskott–Aldrich syndrome protein (WASP) verprolin homologous (WAVE) protein is activated by both the phospholipid PtdIns4,5P2 and by the G protein Rac, which is linked to WAVE through the insulin receptor substrate IRSp53. The cofilin (C) homology and the acidic (A) regions bind actin-related protein 2/3 complex (Arp2/3 complex), which is responsible for actin polymerization that favours a branching pattern as is seen during membrane ruffling. The related WASP protein is regulated by PtdIns4,5P2 and the G protein Cdc42, which binds to the GTPase-binding domain (GBD). The N-terminal C/A domain binds Arp2/3 to initiate actin polymerization, as does the WAVE protein. However, the WASP configuration seems to favour the formation of long filaments to form filopodia.