Two Poles and a Compass Cell Ruedi Meili, Richard A Firtel  Cell  Volume 114, Issue 2, Pages 153-156 (July 2003) DOI: 10.1016/S0092-8674(03)00553-1

Figure 1 Network of Signaling Pathways Outline of the signaling network described in the Bourne and Wu papers (Xu et al, 2003; Li et al, 2003 [both in this issue of Cell, respectively]) connecting chemoattractant receptors with the cytoskeleton. A module responsible for directionality senses external gradients and uses PI3K and Cdc42 to help orient the locomotion module that regulates F actin polymerization. The components that directly facilitate F actin polymerization (WASp, Arp2/3, etc) are not shown. F actin polymerization at the leading edge, which is downstream of Rac, and actomyosin contraction, which is downstream of Rho at the uropod, provide the net translocation force. The biochemical nature of the observed regulatory interactions between these main branches is currently unknown. Some of the arrows stand for multiple only partially characterized steps. Dashed arrows indicate a linkage but the pathways involved have not been elucidated. See the text for details. Cell 2003 114, 153-156DOI: (10.1016/S0092-8674(03)00553-1)

Figure 2 Localization of Signaling Events in a Chemotaxing Cell The spatial localization components described in Figure 1 are shown. The described mediators of directionality (PI3K, PAK1 complex) and of F actin polymerization (Rac, PI3K) are preferentially localized to the leading edge. This is controlled, in part, by Gβγ and, in part, via a positive feedback loop producing PIP3 as a second messenger that in turn is able to recruit and activate additional components. The uropod is characterized by contractile actin/myosin filaments that are regulated by Rho. As in Dictyostelium, PTEN is localized to the plasma membrane at the sides and back but not the front of cells, helping to restrict the PI3K signal to the leading edge. The negative feedback regulation of anterior and posterior pathways assures functional separation. Gi refers to the heterotrimeric G protein containing Gαiβγ. See the text for details. Cell 2003 114, 153-156DOI: (10.1016/S0092-8674(03)00553-1)