Nhe1 is required for directional sensing in vegetative <i>Dictyostelium</i> cell migration

Na+/H+ exchanger 1 (Nhe1) is a crucial regulator of pH homeostasis and the present study demonstrates that Nhe1 is required for directional sensing in vegetative <i>Dictyostelium</i> cell migration. <i>nhe1</i> null cells exhibited severe defects in directional sensing and migration in response to folate gradients and applied electric fields.Specifically, <i>nhe1</i> null cells failed to exhibit proper translocation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to the cell cortex and showed abnormal intracellular calcium signaling upon folate stimulation. Additionally, cells lacking Nhe1 exhibited a reduced capacity to engulf bacteria and latex beads. In contrast, <i>nhe1</i> null cells in the developed stage displayed a defect in cAMP-directed chemotaxis, but normal translocation kinetics of PIP3 to the cell cortex upon cAMP stimulation.