ACRASIN, ACRASINASE, AND SENSITIVITY TO ACRASIN DICTYOSTELIUM DISCOIDEUM

The purpose of this study was to examine the role in normal development of an acrasin (cyclic-AMP) and of an acrasinase (phophodiesterase) and the sensitivity to acrasin in the cellular slime mold Dictyostelium discoideum. Phosphodiesterase is secreted throughout the vegetative, aggregation, and migration stages. It is unclear whether or not cyclic-AMP is produced by vegetative amoebae, but there is a 100-fold increase between the beginning of aggregation and late aggregation, falling to a lower level during migration. The sensitivity to cyclic-AMP also increases 100-fold during aggregation, therefore the chemotactic system is at least 104 times more effective during aggregation than during the vegetative stage. Artificial patterns of amoebae may be produced by making an uneven distribution of cyclic-AMP in the agar with an even distribution of amoebae, or the reverse. The results of these experiments show: (1) the importance of phosphodiesterase in making steep gradients (and providing the basis of various acrasin assays), (2) the role of steep gradients of cyclic-AMP in producing cell adhesiveness, and possibly inhibiting centers; (3) the center-inducing capacity of a high concentration of externally applied cyclic-AMP. It is postulated that prior to normal aggregation, the distribution of chemicals affecting aggregation is homogeneous, and that this equilibrium is upset by sudden excessive sensitivity to cyclic-AMP and its production by certain cells, and the prevention of neighboring cells from having such an increase. The result, by chemotaxis, is an uneven distribution of cells which ultimately reach a new steady state in which they are massed together in groups spaced nonrandomly over the surface of the substratum. © 1969.