Chemotaxis in reverse

Zinc messenger Z inc has always had its fi ngers in the structure and activity of enzymes, transcription factors, and signaling molecules. Now, Yamasaki et al. (page 637) fi nd zinc also working as a second messenger capable of converting an external signal into internal events. When the authors created an external signal in mast cells by cross-linking IgE receptors, they observed an internal wave of free zinc released from the vicinity of the ER. Calcium and activated MAP kinase were necessary for the wave, which took several minutes to occur, in contrast to rapid calcium releases. Cranking up the levels of free zinc prolonged the expression of cytokines IL-6 and TNFα—late stages of IgE signaling—and vice versa. Higher zinc also enhanced tyro-sine phosphorylation levels, so zinc may boost signaling efficiency by inhibiting phos-phatase activity. The precise origin of the wave and how zinc stores are released remain a mystery, as do the downstream targets of the free zinc. Another important step will be to determine whether zinc wave signaling is a general phenomenon or is specifi c to mast cells. The zinc wave could be a potent addition to the cell's limited second messenger repertoire, as 2–3% of total cell proteins have zinc-binding domains. 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 chemoattrac-tants 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 fi laments, 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 …