The FH2 domain of formin proteins is critical for platelet cytoskeletal dynamics

Reorganisation of the actin cytoskeleton is required for proper functioning of platelets following activation in response to vascular damage. Formins are a family of proteins which regulate actin polymerisation and cytoskeletal organisation. Several formin protein are expressed in platelets and so we used an inhibitor of formin mediated actin polymerisation (SMIFH2) to uncover the role of these proteins in platelet spreading. Pre-treatment with SMIFH2 completely blocks platelet spreading in both mouse and human platelets through effects on the organisation and dynamics of actin and microtubules. However, platelet aggregation and secretion are unaffected. SMIFH2 also caused a decrease in resting platelet size and disrupted the balance of tubulin post-translational modification. These data therefore demonstrated an important role for formin mediated actin polymerisation in platelet spreading and highlighted their importance in cross talk between the actin and tubulin cytoskeletons. Key Points Inhibition of FH2 domains blocks platelet spreading and disrupts actin and microtubule organisation Inhibition of FH2 domains causes a reduction in resting platelet size but not by microtubule coil depolymerisation FH2 domains play a role in the post-translational modification of microtubules Visual abstract