Meta-Biol

• Pathways

Neural Wiskott-Aldrich syndrome protein (WASL, N-WASP) is a scaffold protein that transduces signals from cell surface receptors to the activation of the ARP2/3 complex and actin polymerization. N-WASP possesses a central GTPase binding domain (GBD) and an NH2-terminal WASP homology domain 1 (WH1). Adjacent to this is a basic region (B) and a C-terminal containing VCA region that contains a V domain (verprolin homology/WASP homology 2), a C domain (connecting), and an A motif (acidic). The VCA region is responsible for binding to and activating the ARP2/3 complex (Bompard & Caron 2004, Callebaut et al. 1998). Under resting conditions, N-WASP is maintained in an auto-inhibition state via interaction of the N-terminal GBD and the C-terminal VCA domains. This prevents access of the ARP2/3 complex to the VCA region. Activated CDC42 binds to the GBD region in N-WASP and this interaction releases the VCA region from auto-inhibition enabling binding of the ARP2/3 complex stimulating actin polymerization (Kim et al. 2000, Park & Cox 2009). Phosphoinositides (PtdIns(4,5)P2) interact with the basic (B) region in WASP and this interaction is important for activation of the WASP and ARP2/3 complex (Higgs & Pollard 2000).