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. 2020 Jun 16;12:22. doi: 10.3389/fnsyn.2020.00022

Figure 1.

Figure 1

Regulation of actin organization by Rho family GTPases. Rac and Cdc42 promote F-actin polymerization via stimulation of p21-activated kinases (PAKs), which phosphorylate and activate LIM kinase-1 (LIMK1). Rho activates LIMK1 by stimulating its downstream kinase ROCK, which phosphorylates LIMK1 directly. Active LIMK1 inhibits cofilin-mediated severing of actin filaments by phosphorylating cofilin on serine-3. Cofilin is re-activated upon dephosphorylation of serine-3 by the phosphatase, slingshot (SSH). SSH is inactivated by CaMKII-mediated phosphorylation, triggered by high-frequency stimulation (HFS) and re-activated upon dephosphorylation by calcineurin, triggered by low-frequency stimulation (LFS). Rac and Cdc42 promote actin branching by activating the nucleation promoting complexes WAVE and WASP, which stimulate the actin filament nucleating activity of the Arp2/3 complex. Rac activation of WAVE is facilitated by binding to the adaptor, IRSp53.