Signalling to actin assembly via the WASP (Wiskott-Aldrich syndrome protein)-family proteins and the Arp2/3 complex.
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.
Millard
Thomas H
TH
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Sharp
Stewart J
SJ
Machesky
Laura M
LM
D008841:Actin Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008958:Models, Molecular; D009024:Morphogenesis; D010940:Plant Proteins / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein
C495926:ACTR2 protein, human; C495928:ACTR3 protein, human; D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; C495927:Actr2 protein, mouse; C495929:Actr3 protein, mouse; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D010940:Plant Proteins; D011506:Proteins; D015800:Protozoan Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C495767:WAS protein, human; C495768:Was protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D000255:Adenosine Triphosphate