Actin nucleation-promoting factor WASL belongs to the WASP family, whose members signal to the cytoskeleton through the Arp2/3 complex, an actin-nucleating assembly that regulates the structure and dynamics of actin filament networks at the leading edge of the cell []. WASP family members have unique N-terminal regions, followed by a central segment rich in proline, and a common C-terminal region. Their conserved C-terminal VCA domain consists of two WH2 (WASP homology 2) domains ("V"referring to either a single or multiple WH2 domains), followed by a connector domain ("C") and an acidic short extension ("A"). In the VCA region, the WH2 domain(s) bind G-actin, whereas the CA domain binds Arp2/3 complex []. Their distinct N-terminal region enables family members to activate Arp2/3 in response to different upstream signals.Interestingly, pathogen such as enteropathogenic Escherichia coli can affect host cell Arp2/3-dependent actin assembly through injecting a bacterial protein, translocated intimin receptor (Tir), into the host cell [, ]. Tir binds to the host-cell adaptor protein Nck. Nck interacts with a complex of WIP and N-WASP, resulting in the activation of the Arp2/3 complex and actin polymerisation []. Vaccinia virus can also affect actin assembly in the host cells through the interaction between its transmembrane protein A36 and host proteins, such as Grb2, Nck, WIP and N-WASP. Arp2/3-induced actin polymerisation propels the virus away from the cell surface towards neighbouring cells, enhancing the spread of infection [].
WAS/WASL-interacting protein family member 2 (WIPF2, also known as WICH or WIRE) contains a verprolin-homology (V) region. It plays an important role in actin-microspike formation through cooperation with WASL (neural Wiskott-Aldrich syndrome protein, also known as N-WASP) []. It plays an active role in the formation of cell surface protrusions downstream of activated PDGFB (platelet-derived growth factor B) receptors [].
