The actin-related protein 2/3 (ARP2/3) complex nucleates branched actin networks. During cell migration, it is activated at the leading edge of cells to power the protrusion of the plasma membrane in lamellipodia. The small GTPase RAC directly activates the WAVE complex, which in turn activates the ARP2/3 complex. As proteins that contain an acidic motif inhibit ARP2/3 at other locations in the cell, Dang et al. performed a bioinformatics search for proteins with such a motif that might counteract WAVE at lamellipodia. They identified Arpin, which binds to ARP2/3 via the acidic motif to inhibit actin polymerization and is also activated by RAC. Thus, RAC signalling induces both activation and repression of ARP2/3 at lamellipodia. The inhibitory activity of Arpin has a steering function: cells depleted of Arpin migrated faster and straighter, whereas microinjection of Arpin in cells that normally move with straight trajectories led them to turn.
References
Dang, I. et al. Inhibitory signalling to the Arp2/3 complex steers cell migration. Nature http://dx.doi.org/10.1038/nature12611 (2013)
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Baumann, K. Putting a brake for cells to turn. Nat Rev Mol Cell Biol 14, 753 (2013). https://doi.org/10.1038/nrm3712
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DOI: https://doi.org/10.1038/nrm3712