LeClaire et al. show that the decision is more complex than previously thought.
A cell slithers by extending a membrane protrusion, or lamellipodium, driven by newly assembled actin filaments. A seven-part protein complex called Arp2/3 controls the lengthening and branching of these filaments. Researchers thought that binding of a pair of so-called nucleation promoting factors, WASP and Scar, was sufficient to switch on Arp2/3. However, LeClaire et al. determined that phosphorylation of Arp2/3's subunits also was essential for the complex's activation—and thus for actin elongation and lamellipodia extension.
Arp2/3 works by attaching to the side of an existing actin filament and then spurring a branch to grow. To nail down which action phosphorylation controls, the team used several methods to dislodge phosphates. After treatment Arp2/3 could still grab hold of an actin fiber, but it couldn't perform capping, an essential step that prevents the newly formed actin filament from breaking apart. The cells also could not extend lamellipodia.
The work suggests that Arp2/3 serves as a command center, receiving input not just from WASP and Scar, but also from phosphate-adding enzymes. The researchers think that this complexity provides the cell with more precise control over its movement.