A repellent on the right causes a Dictyostelium cell (b) to move to the left by raising PIP3 levels on the opposite side.

A cell polarity switch controls whether cells rush toward an attractive chemical or shift into reverse when they encounter something repulsive, according to Keizer-Gunnink et al. on page 579. They show that the status of phospholipase C (PLC) sets up the polarity axis for directional movement.

As professional crawlers, Dictyostelium cells had previously revealed that chemoattractants cause a PIP3 build-up on that side of the cell, which in turn induces the actomyosin motility machinery. Now, the authors show that the same crawlers hold the keys to chemorepulsion.

When faced with a repellent, the cells built up PIP3 on the opposite side of the cell, inducing the motility machinery to reverse direction. Attractants and repellents caused PIP3 levels to rise on opposite sides of the cell using a symmetry break established by the mutually exclusive locations of the enzymes that produce and degrade PIP3.

The producing enzyme, PI3 kinase, hangs out at sites of PIP3-induced actin filaments, whereas the degrading enzyme, PTEN, binds to its product, PIP2. The two therefore do not cross paths in the cell.

To back up, cells increased PIP2 levels at the leading edge. Repellents inactivated the PIP2 destroyer, PLC, at the near edge, thus allowing PIP2 to accumulate there. The PIP2 then recruited PTEN to the front, thereby concentrating most PIP3 in the rear of the cell for a getaway. Chemoattractants, in contrast, activated PLC. Whether repulsion works the same in nature—by mammalian cells during development or by Dictyostelium cells warding off hungry neighbors during starvation—remains unknown.