ATP hydrolysis by the Arp2/3 complex promotes the disassembly of lamellipodial actin networks, Ingerman et al. reveal.
The Arp2/3 complex generates branched actin networks and lamellipodial cell protrusions by nucleating new actin filaments from the sides of preexisting ones. The complex contains two actin-related proteins, Arp2 and Arp3, that bind ATP in a conserved nucleotide-binding pocket, like actin itself. ATP hydrolysis by actin destabilizes polymerized actin filaments, but the effect of ATP hydrolysis by Arp2 and Arp3 remains unclear.
Ingerman et al. made hydrolysis-defective versions of Arp2 and Arp3. These mutants were still able to nucleate actin filaments and support the assembly of branched actin networks in cells. But hydrolysis-defective Arp2/3 complexes took longer to dissociate from actin filaments, thereby delaying—but not preventing—network turnover. Complexes containing mutant versions of both Arp2 and Arp3 were even slower to initiate network disassembly than complexes containing just one hydrolysis-defective subunit, indicating that Arp2 and Arp3 have independent roles in network turnover.
Hydrolysis-deficient Arp2/3 complexes were also able to assemble branched actin networks in vitro, and these networks were more resistant to disassembly by the actin-severing protein cofilin. The researchers now want to investigate how cofilin and related proteins contribute to the disassembly of lamellipodial actin networks and to determine how their activities are coordinated with ATP hydrolysis by actin and the Arp2/3 complex.
Text by Ben Short