title: Diverse sensitivity thresholds in dynamic signaling responses by social amoebae.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Clark Hall Room 207, Baltimore, MD 21218, USA.
authors.forename: C Joanne
authors.initials: CJ
authors.lastname: Wang
authors.forename: Adriel
authors.initials: A
authors.lastname: Bergmann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lin
authors.forename: Kyuri
authors.initials: K
authors.lastname: Kim
authors.forename: Andre
authors.initials: A
authors.lastname: Levchenko
mesh_terms: D002630:Chemotactic Factors / Q000378:metabolism* / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D002630:Chemotactic Factors; D000242:Cyclic AMP