Biochemical Journal

Review article

Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex

Thomas H. MILLARD, Stewart J. SHARP, Laura M. MACHESKY


The assembly of a branched network of actin filaments provides the mechanical propulsion that drives a range of dynamic cellular processes, including cell motility. The Arp2/3 complex is a crucial component of such filament networks. Arp2/3 nucleates new actin filaments while bound to existing filaments, thus creating a branched network. In recent years, a number of proteins that activate the filament nucleation activity of Arp2/3 have been identified, most notably the WASP (Wiskott–Aldrich syndrome protein) family. WASP-family proteins activate the Arp2/3 complex, and consequently stimulate actin assembly, in response to extracellular signals. Structural studies have provided a significant refinement in our understanding of the molecular detail of how the Arp2/3 complex nucleates actin filaments. There has also been much progress towards an understanding of the complicated signalling processes that regulate WASP-family proteins. In addition, the use of gene disruption in a number of organisms has led to new insights into the specific functions of individual WASP-family members. The present review will discuss the Arp2/3 complex and its regulators, in particular the WASP-family proteins. Emphasis will be placed on recent developments in the field that have furthered our understanding of actin dynamics and cell motility.

  • actin
  • Arp2/3 complex
  • nucleation
  • suppressor of the cAMP receptor (Scar)
  • WASP-family verprolin homologous protein (WAVE)
  • Wiskott—Aldrich syndrome protein (WASP)


  • Abbreviations used: A, acidic; Abi-2, abl-interactor 2; ADF, actin-depolymerizing factor; Arp, actin-related protein; ARPC, Arp2/3 complex component; B, basic; C, central; cAR, cyclic AMP receptor; CARMIL, capping protein, Arp2/3 and myosin Ilinker; CRIB, Cdc42 and Rac interactive binding; EGF, epidermal growth factor; EVH1, Ena (Drosophila enabled)/VASP (vasodilator-stimulated phosphoprotein) homology 1; GAP, GTPase-activating protein; GEF, guanine-nucleotide exchange factor; HSPC300, haematopoietic stem progenitor cell 300; IRS, insulin receptor substrate; Nap125, Nck-associated protein with an Mr of 125 000; N-WASP, neural Wiskott–Aldrich syndrome protein; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP5K, phosphatidylinositol phosphate 5-kinase; PIR121, p53-inducible mRNA with an Mr of 140000; RNAi, RNA-mediated interference; Scar, suppressor of the cAR; SH2, src homology 2; SH3, src homology 3; SHD, Scar homology domain; WAVE, WASP-family verprolin homologous protein; WCA, WH2, central and acidic domains; WH1, WASP homology 1; WH2, WASP homology 2; WIP, WASP-interacting protein.