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.
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: Daniel J Marston; Karen L Anderson; Mark F Swift; Marie Rougie; Christopher Page; Klaus M Hahn; Niels Volkmann; Dorit Hanein Journal: Proc Natl Acad Sci U S A Date: 2019-01-10 Impact factor: 11.205
Authors: Sofia Espinoza-Sanchez; Lauren Ann Metskas; Steven Z Chou; Elizabeth Rhoades; Thomas D Pollard Journal: Proc Natl Acad Sci U S A Date: 2018-08-27 Impact factor: 11.205
Authors: Luke A Helgeson; Julianna G Prendergast; Andrew R Wagner; Max Rodnick-Smith; Brad J Nolen Journal: J Biol Chem Date: 2014-08-26 Impact factor: 5.157