Increasing amounts of Ena/VASP (left to right) change the actin architecture.



More actin-based protrusion should mean more cell movement, or so it has been thought. Yet depletion of the Ena/VASP family of actin-binding proteins, which promote lamellipodial protrusion rates, actually causes cells to move faster. New results from James Bear, Tatyana Svitkina, Frank Gertler (MIT, Cambridge, MA), and colleagues explain this counterintuitive effect by putting the emphasis on the quality rather than the quantity of protrusions.

The group boosted Ena/VASP levels at the plasma membrane of fibroblasts and saw increases in protrusion velocity. But the protrusions were quickly withdrawn as ruffles. Within these lamellipodia, actin filaments were longer and less branched than normal and ran parallel to the membrane instead of perpendicular. “This tells us that the geometry of actin polymerization is critical for regulating the rate and stability of protrusions,” says Gertler.

Depletion of Ena/VASP had the opposite effect: the cells made shorter, more highly branched actin filament networks and had slower and more persistant protrusions. These are the cells that move more quickly. “The simplest viewpoint was that promoting actin assembly should increase the rate of cell movement,” says Gertler. “But it's not that simple–you must look at the separate components of cell motility.” These include the rate of protrusion extension, the stability and adhesion of protrusions, cell contraction, and cell polarity. Gertler found that the duration, rather than the rate, of protrusions best correlated with translocation speed.

The Ena/VASP proteins bind to the barbed ends of actin filaments and antagonize the activity of capping proteins while allowing filament extension. This makes Ena/VASP the first anti- capping proteins identified. The inhibition of protrusion by Ena/VASP could be reversed by cytochalasin D treatment, indicating that the critical parameter is filament length, rather than branching. Filaments that are too long will extend along the membrane, whereas shorter filaments can push against the membrane as they polymerize. ▪


Bear, J., et al.