Figure 10. Scheme of the regulation of actin turnover by LIM kinase (LIMK)/cofilin in WT and type 2B mutant vWF/p.V1316M (2B) megakaryocytes (MKs).

LIMKs influence the architecture of the actin cytoskeleton by regulating the activity of the cofilin family proteins. In WT mice, the equilibrium between nonphosphorylated and phosphorylated cofilin stimulates severance and depolymerization of actin, and promotes actin filament turnover, leading to proper platelet production. By contrast, in 2B MKs, the inactivation of cofilin by phosphorylation at Ser3 is upregulated. This leads to cofilin losing its ability to bind actin and then suppresses actin turnover (2). RhoA/ROCK regulates the LIMK/cofilin pathway in WT MKs and is upregulated in 2B MKs. ROCK, RhoA kinase.