Cells detect chemical gradients (chemoattractants) and engage intracellular signal transduction pathways to prompt the cell to polarise and migrate up the gradient. This ability, called chemotaxis, must be under precise spatial and temporal control. Ras family GTPases, such as RasG, RasC and Rap1, mediate the chemotactic response to the chemoattractant by regulating cell polarity and the actin cytoskeleton. However, the detailed regulatory mechanisms to activate and control chemotaxis are not well understood. Now (p. 1545), Pascale Charest and colleagues report on the role of protein kinase A (PKA) in this process in Dictyostelium discoideum. Loss of PKA leads to the misregulation of the actin cytoskeleton and severe defects in sensing of the chemotactic gradient. The authors perform a set of experiments that suggest a direct role for PKA in the chemotactic signal transduction pathways, besides its known requirement for the transcriptional control of genes involved in chemotaxis. Interestingly, the lack of PKA results in altered activity of those Ras family GTPases that are positioned upstream of PKA in the transduction pathway. This study therefore provides evidence for a new role for PKA in establishing a negative-feedback mechanism that controls the early spatiotemporal regulation of the chemoattractant signal.
