Collaboration of Antipodes: Synergy of Branched and Linear F-Actin during Amoeboid Cell Movement and Chemotaxis

The actin cytoskeleton plays a major role in locomotion of amoeboid cells. The extending pseudopod contains predominantly branched F-actin nucleated by actin-related protein 2/3 (Arp2/3) that is oriented toward the membrane, while the side/back of the cell contains predominantly linear F-actin nucleated by formins that is arranged parallel to the membrane in a contractile network using cross-linkers, membrane anchors, and myosin filaments. During cell movement, branched and linear F-actin have opposite functions: Elongation of branched F-actin filaments leads to pseudopod growth in the front, whereas pseudopod formation is strongly inhibited in areas of the contractile network. On the other hand, branched and linear F-actin also collaborate to optimize locomotion and navigation. Assembly of branched F-actin to induce a new pseudopod in the front also activates linear F-actin in the rest of the cell to inhibit a second pseudopod. Furthermore, linear F-actin at the side/back of the cell and branched F-actin each provide a memory of direction that is highly synergistic to mediate strong persistence of cell movement and sensitive chemotaxis.