Unlike preschoolers, cells are good about sharing. They swap ions, nutrients, and other molecules via membrane channels called gap junctions. But on page 881, van Zeijl et al. show that local loss of a phospholipid permits cells to become selfish and shut the channels.

Open gap junctions are crucial for heart contraction, wound repair, and other functions. But cells can temporarily shut the channels—when injured, for instance—and cancer cells can shut them permanently. G protein–coupled receptors close these portals, which are often made from the protein connexin43. But how that closure happens was unclear.

G protein–coupled receptors latch onto the enzyme PLCβ, which in turn slices up the membrane phospholipid PIP2. The researchers found that blocking PLCβ or cranking up PIP2 production kept the channels open, suggesting that PIP2's digestion helped close them. To confirm the conclusion, van Zeijl et al. used a two-part, PIP2-cutting enzyme that assembles on the membrane only after a dose of the drug rapamycin. Adding the compound shut gap junctions.

How PIP2 influences channels was initially mysterious, as it did not attach to connexin43. But the group discovered that PLCβ hooked onto the protein ZO-1, which does link to connexin43. The results suggest a mechanism in which ZO-1 positions PLCβ so that it can chop up PIP2 near connexin43. The next step remains unclear. Presumably, PIP2 breakdown stimulates a protein that nudges the junction closed, but its identity is unknown.