PI3K (arrows) accumulates in the stretching pseudopods of a slithering cell.

Hungry cells often wander around, hunting for something tasty. On page 185, Sasaki et al. tease out a molecular circuit that activates spontaneously and initiates these random movements.

Slime mold cells make a beeline for their bacterial food, and researchers have dissected the pathway that controls this directional travel. Bacterial molecules prod G-protein–coupled receptors on the cell surface, leading to activation of the proteins Ras and PI3K. In turn, PI3K cranks out PIP3, which spurs actin molecules to polymerize and push the cell membrane forward. But scientists didn't know what governs cells' random crawling in search of food.

Many of the same molecules participate, Sasaki et al. learned when they studied slime mold cells that lack G-protein–coupled receptor signaling. Ras and PI3K switched on, PIP3 formed, and cell extensions elongated as the result of actin polymerization.

The team also found that Ras and PI3K turn on at the same sites on the cell membrane where new extensions sprout. PI3K can't switch on without Ras, and vice versa, suggesting that the two molecules are locked into a positive feedback loop. The findings indicate that aimless crawling is under control of a molecular circuit that fires without external stimulation. The randomness occurs, the scientists speculate, because components of the loop such as Ras show a low but fluctuating level of activity. Any increase in activity at a particular location on the membrane gets amplified by positive feedback, triggering the cell to move in that direction.