Macropinocytosis is a widely conserved actin-dependent mechanism by which eukaryotic cells can engulf large volumes of extracellular fluid and dissolved molecules. Fluid uptake in Dictyostelium amoebae occurs almost entirely by macropinocytosis, so Dictyostelium is becoming a leading model for the study of this process. To further develop this model, Thomas Williams and Robert Kay now describe a high-throughput flow cytometry assay to measure fluid uptake by Dictyostelium, and use this method to determine the physiological context for macropinocytosis in Dictyostelium (Williams and Kay, 2018). The authors examine the effect of inhibitors on macropinocytosis, confirming previous genetic studies that show that the macropinocytosis depends on PI3K, Rac and actin dynamics controlled through SCAR/WAVE, WASP and formins. The authors show that Dictyostelium has two basic feeding modes: phagocytic and macropinocytic. Phagocytosis is the preferred mode of feeding, and cells maintain the ability to phagocytose regardless of nutritional context. Macropinocytosis occurs at a high rate in Dictyostelium in liquid medium, but cells can adapt to growth conditions, transitioning slowly between high and low macropinocytic states according to whether bacteria or soluble nutrients – arginine, lysine, glutamate and sugar – are available. Moreover, the authors find that downregulation of macropinocytosis during early development requires a developmental signal that most likely acts through PKA. These findings further our understanding of macropinocytosis and its mechanistic relation to phagocytosis.
