Correlated waves of actin filaments and PIP₃ in Dictyostelium cells

Chemotaxis-deficient amiB-null mutant Dictyostelium cells show two distinct movements: (1) they extend protrusions randomly without net displacements; (2) they migrate persistently and unidirectionally in a keratocyte-like manner. Here, we monitored the intracellular distribution of phosphatidylinositol (3,4,5)-trisphosphate (PIP₃) to gain insight into roles PIP ₃ plays in those spontaneous motilities. In keratocyte-like cells, PIP₃ showed convex distribution over the basal membrane, with no anterior enrichment. In stalled cells, as well as in wild type cells, PIP ₃ repeated wave-like changes, including emergence, expansion and disappearance, on the basal membrane. The waves induced lamellipodia when they approached the cell edge, and the advancing speed of the waves was comparable to the migration speed of the keratocyte-like cells. LY294002, an inhibitor of PI3 kinase, abolished PIP₃ waves in stalled cells and stopped keratocyte-like cells. These results together suggested that keratocyte-like cells are "surfing" on the PIP₃ waves by coupling steady lamellipodial protrusions to the PIP₃ waves. Simultaneous live observation of actin filaments and PIP₃ in wild type or stalled amiB^- cells indicated that the PIP₃ waves were correlated with wave-like distributions of actin filaments. Most notably, PIP₃ waves often followed actin waves, suggesting that PIP₃ induces local depolymerization of actin filaments. Consistent with this idea, cortical accumulation of PIP₃ was often correlated with local retraction of the periphery. We propose that the waves of PIP₃ and actin filaments are loosely coupled with each other and play important roles in generating spontaneous cell polarity.