Phosphatidylinositol 3-kinases play a suppressive role in cell motility of vegetative Dictyostelium cells

Abstract

Phosphatidylinositol 3-Kinase (PI3K) is a key regulator of cell motility during chemotaxis and plays an important role in relaying and amplifying the shallow gradient of chemoattractant signals to ultimately mediate rearrangements of the actin cytoskeleton. To determine whether PI3K plays a similar role in electrotaxis as in chemotaxis, we examined directional cell migration in response to an electric field (EF) and unexpectedly found that the role of PI3K in regulating cell motility differs depending on the state of Dictyostelium cells. Contrary to chemotaxis experiments using aggregation-competent cells, in the cell migration assay, we used a recently developed method for electrotaxis using 3-h starved cells. Wild-type cells starved for 3 h showed increased motility in the presence of LY294002, a PI3K inhibitor, whereas aggregation-competent cells showed slightly decreased motility, indicating the effect of LY294002 on cell motility differ depending on the state of the cells. Consistent with these results, pi3k null cells in the vegetative state exhibited increased motility similar to that in the presence of LY294002, compared to wild-type cells. These findings were confirmed through random migration experiments. These results suggest that PI3Ks play a suppressive role in regulating cell motility of vegetative Dictyostelium cells and that the suppressive effect is reversed on inhibition or lack of PI3Ks, leading to high motility.