title: Dip1 defines a class of Arp2/3 complex activators that function without preformed actin filaments.
abstract: BACKGROUND
  Arp2/3 complex is a key actin cytoskeletal regulator that creates branched actin filament networks in response to cellular signals. WASP-activated Arp2/3 complex assembles branched actin networks by nucleating new filaments from the sides of pre-existing ones. WASP-mediated activation requires seed filaments, to which the WASP-bound Arp2/3 complex can bind to form branches, but the source of the first substrate filaments for branching is unknown.
  
  
  RESULTS
  Here we show that Dip1, a member of the WISH/DIP/SPIN90 family of actin regulators, potently activates Arp2/3 complex without preformed filaments. Unlike other Arp2/3 complex activators, Dip1 does not bind actin monomers or filaments, and it interacts with the complex using a non-WASP-like binding mode. In addition, Dip1-activated Arp2/3 complex creates linear instead of branched actin filament networks.
  
  
  CONCLUSIONS
  Our data show the mechanism by which Dip1 and other WISH/DIP/SPIN90 proteins can provide seed filaments to Arp2/3 complex to serve as master switches in initiating branched actin assembly. This mechanism is distinct from other known activators of Arp2/3 complex.
authors.affiliation: Institute of Molecular Biology and Department of Chemistry and Biochemistry, University of Oregon, Eugene, OR 97403, USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Wagner
authors.forename: Qing
authors.initials: Q
authors.lastname: Luan
authors.forename: Su-Ling
authors.initials: SL
authors.lastname: Liu
authors.forename: Brad J
authors.initials: BJ
authors.lastname: Nolen
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051376:Actin-Related Protein 2-3 Complex / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D051376:Actin-Related Protein 2-3 Complex; C000588753:Dip1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins