Fig. 9. (A) Model of Dictyostelium signaling pathways involved in shear stress-induced motility. Experimental evidence supporting a role for PI3K in the directionality response is presented elsewhere (Décavé et al., 2003). A link between mechanical stress and heterotrimeric G protein activation is shown in the present work since Gß-invalidation reduces cell speed in response to shear stress (Fig. 6C). In both cases, molecular details are unknown. Heterotrimeric G protein mediated Ca²⁺ entry (arrows 1 and 2) is supported by the effect of Gd³⁺ ions (Fig. 1D) and Gß-invalidation (Fig. 6B). Ca²⁺-induced PLC activation (arrow 3) is shown in (Cubitt and Firtel, 1992). Direct biochemical evidence for IP₃-mediated calcium release (arrows 4 and 5) is given elsewhere (Schaloske et al., 2000). Our work suggests Dictyostelium IP₃-receptor-like protein as a possible mediator (Fig. 8). The link between intracellular calcium and cell speed is shown in our work and (Van Duijn and Van Haastert, 1992). Note that calcium pumping activities, which are essential to restore low cytosolic calcium concentrations, are omitted. (B,C) Protrusive and retractile activities of cell-substrate contact area as a function of cell speed. Data are gathered from Fig. 5 (Ax2 cells), Fig. 7 (LW6 and LW20 cells) and from data obtained with IP₃-receptor null cells (not shown). In B, the solid line is a linear least square fit of all data points (slope 9.2 µm; ordinate at origin 0.84 µm² second^-1). In C, solid and dotted lines are linear least square fits of protrusion and retraction frequencies (slope -0.03 and -0.02 µm^-1, respectively; ordinate at origin 0.13 and 0.09 Hz, respectively).