Diverse Sensitivity Thresholds in Dynamic Signaling Responses by Social Amoebae

Dictyostelium cells with increased responsiveness to chemoattractant may promote propagation of the initial signal across the cell population. Genetically Identical, But Not Equally Sensitive Individual cells of the social amoeba Dictyostelium can organize to form multicellular ensembles, a process in which the chemoattractant cAMP (cyclic adenosine monophosphate) triggers production of phosphatidylinositol 3,4,5-trisphosphate (PIP3) to induce polarization of the chemotaxing cells. Cell population responses have generally been averaged; however, Wang et al. found that not all cells in a group of genetically identical Dictyostelium cells produced PIP3 in response to cAMP and that more cells produced PIP3 as the cAMP concentration increased. Furthermore, modeling and experiments suggested that an amplification step occurred downstream of an adaptive signaling network and that different cells had different amplification thresholds. Different sensitivities and thresholds for signal amplification may enable highly responsive individual cells to promote chemotaxis of an entire population of Dictyostelium cells and, thus, mediate collective behavior. The complex transition from a single-cell to a multicellular life form during the formation of a fruiting body by the amoeba Dictyostelium discoideum is accompanied by a pulsatile collective signaling process that instigates chemotaxis of the constituent cells. Although the cells used for the analysis of this phenomenon are normally genetically identical (isogenic), it is not clear whether they are equally responsive to the waves of the signaling stimulus, nor is it clear how responses across the population influence collective cell behavior. Here, we found that isogenic Dictyostelium cells displayed differing sensitivities to the chemoattractant cyclic adenosine monophosphate (cAMP). Furthermore, the resulting signaling responses could be explained by a model in which cells are refractory to further stimulation for 5 to 6 min after the initial input and the signaling output is amplified, with the amplification threshold varying across the cells in the population. This pathway structure could explain intracellular amplification of the chemoattractant gradient during cell migration. The new model predicts that diverse cell responsiveness can facilitate collective cell behavior, specifically due to the presence of a small number of cells in the population with increased responsiveness that aid in propagating the initial cAMP signaling wave across the cell population.