Dip1 Defines a Class of Arp2/3 Complex Activators that Function without Preformed Actin Filaments

• Published in: Current biology Vol. 23; no. 20; pp. 1990 - 1998
• Main Authors: Wagner, Andrew R., Luan, Qing, Liu, Su-Ling, Nolen, Brad J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 21.10.2013
• Subjects: actin; Actin Cytoskeleton - metabolism; Actin-Related Protein 2-3 Complex - genetics; Actin-Related Protein 2-3 Complex - metabolism; Amino Acid Sequence; binding proteins; Electrophoresis, Polyacrylamide Gel; Immunoblotting; microfilaments; Microscopy, Fluorescence; Molecular Sequence Data; regulator genes; Schizosaccharomyces - genetics; Schizosaccharomyces - metabolism; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Sequence Alignment; transcription factors
• ISSN: 0960-9822; 1879-0445; 1879-0445
• DOI: 10.1016/j.cub.2013.08.029

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. 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. 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. •Dip1 is a potent activator of Arp2/3 complex•Dip1-mediated activation of Arp2/3 complex does not require preformed actin filaments•Dip1 mechanism may allow it to provide seed filaments for branched network assembly•The mechanism of Dip1 is conserved in the WISH/DIP/SPIN90 family