SMIFH2 inhibition of platelets demonstrates a critical role for formin proteins in platelet cytoskeletal dynamics

Hannah L. H. Greenwood, Malou Zuidscherwoude, Fawaz Alenazy, Christopher Smith, Markus Bender, Steven Thomas

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
144 Downloads (Pure)


Background: Reorganization of the actin cytoskeleton is required for proper functioning of platelets following activation in response to vascular damage. Formins are a family of proteins that regulate actin polymerization and cytoskeletal organization via a number of domains including the FH2 domain. However, the role of formins in platelet spreading has not been studied in detail. Objectives: Several formin proteins are expressed in platelets so we used an inhibitor of FH2 domains (SMIFH2) to uncover the role of these proteins in platelet spreading and in maintenance of resting platelet shape. Methods: Washed human and mouse platelets were treated with various concentrations of SMIFH2 and the effects on platelet spreading, platelet size, platelet cytoskeletal dynamics, and organization were analyzed using fluorescence and electron microscopy. Results: Pretreatment with SMIFH2 completely blocks platelet spreading in both mouse and human platelets through effects on the organization 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. Conclusions: These data therefore demonstrated an important role for formin-mediated actin polymerization in platelet spreading and highlighted the importance of formins in cross-talk between the actin and tubulin cytoskeletons.

Original languageEnglish
Pages (from-to)955-967
JournalJournal of Thrombosis and Haemostasis
Issue number4
Early online date13 Jan 2020
Publication statusE-pub ahead of print - 13 Jan 2020


  • SMIFH2
  • actin
  • blood platelets
  • formin
  • tubulin

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'SMIFH2 inhibition of platelets demonstrates a critical role for formin proteins in platelet cytoskeletal dynamics'. Together they form a unique fingerprint.

Cite this