Figure 2.

Mechanism of initiation of lamellipodia and ruffles. (A,B) Growth factors (GFs) activating receptor tyrosine kinases (RTKs) and other motogenic signals lead to the activation of the small GTPases Rac and Rho. (C) Active, GTP-bound Rho and Rac recruit mDia1 and the WAVE complex to the plasma membrane. Direct binding to Rho changes mDia1's conformation thereby converting it into the actin nucleation-proficient state. Similarly, a physical interaction between Rac and the WAVE complex results in the exposure of the VCA region of WAVE, which can then bind and prime the Arp2/3 complex. (D,E) mDia1 polymerizes linear actin filaments that can be used as a template by WAVE-primed Arp2/3 complex. (F) The Arp2/3 complex assembles the first actin branch thereby initiating lamellipodia and ruffles. Key proteins and complexes are not drawn in scale and are decoded in the box. Note that all WAVE-complex subunits but HSPC300, as well as the domains of WAVE, are depicted in the cartoon.