FIGURE 2.

Profilin-dependent mechanisms in coordinating different actin networks vary in a cell type-specific manner. Fission yeast (left panel): Profilin balances ARP2/3 and Formin-dependent actin networks by directing G-Actin toward formins enabling normal contractile ring development and, thus, normal cytokinesis. Under semi-permissive temperatures, PFN mutants show large actin patches by increased ARP2/3 activity and impaired contractile ring formation and cytokinesis defects according to formin dysfunctions (Suarez et al., 2015). Mouse Fibroblasts (center panel): Wildtype fibroblasts form normal lamellipodia and filopodia. An acute depletion of PFN leads to increased F-Actin levels and formation of prominent ARP2/3-rich lamellipodia. Filopodia formation is impaired in PFN1-depleted fibroblasts. ARP2-deficient fibroblasts exhibit prominent filopodia but no lamellipodia. Actin dynamics in ArpC2-deficient cells rely on PFN1 and Ena/VASP-proteins (Rotty et al., 2015). CAD cells (right panel): PFN deficiency disrupts the actin networks in leading edges of CAD cells by rendering Mena/VASP proteins inactive and displacing the Arp2/3 complex. Rescue experiments with low to medium levels of PFN1 mediate exclusively linear actin filaments and filopodia formation by high Mena/VASP-activity. High levels of profilin in these settings evoke both high Arp2/3 and Mena/VASP activity. Thus, dense branched actin arrays are formed along with linear actin bundles. The latter resembled filopodia precursors while actual filopodia were not formed (Skruber et al., 2020).