ATP Mediates Yeast Cell-Cell Communication

Yeast secrete ATP in response to glucose, a property with previously unknown functional consequence. In this report, we show that extracellular ATP is a signal for growth of surrounding cells. The ATP signaling behavior was serendipitously uncovered by finding reduced toxicity of an inducible, dominant-lethal form of alpha tubulin (tub1-828); lethality was dramatically reduced in cultures grown at high, compared to low cell density. Reduced cell death at high cell density occurred because the mutant tubulins deleterious effect of mitosis was reduced such that the rate of chromosome loss/cell division was lower (18-fold) in cultures inoculated with a high density (75,000/ml) compared to a low density (1,000/ml) of cells. The sparing effect of growth at high cell density could be replicated by co-culturing a low number of cells (3440/5 ml) that expressed tub1-828, with a high number of cells (2.3 E6/5 ml) that did not express the mutant protein. In this condition toxicity was reduced at high cell density apparently because it produced a sufficient concentration of a secreted growth substance, such that the mutant protein was rapidly diluted by synthesis of wild-type alpha tubulin (TUB1). Enhanced growth at high cell density was confirmed by fluorescence-activated cell sorting (FACS) analysis after DNA staining, which showed that the rate of the G1-G2 transition was faster for cells at high density. ATP replaced the need for high cell density for resistance to tub1-828, and stimulated the transition from G1 to G2 in cells at low density. This newly discovered quorum sensing response in yeast, mediated by ATP, indicates that yeast decision-making is not entirely autonomous.