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HDAC6 controls the kinetics of platelet activation

Karin Sadoul, Jin Wang, Boubou Diagouraga, Anne-Laure Vitte, Thierry Buchou, Thérèse Rossini, Benoît Polack, Xiaodong Xi, Patrick Matthias and Saadi Khochbin

Abstract

HDAC6, a major cytoplasmic deacetylase, is shown here to fine-tune the kinetics of platelet activation, a process, which must be precisely regulated to ensure haemostasis after blood vessel injury while preventing pathological thrombus formation. The discoid shape of resting platelets in the circulation is maintained by several, highly acetylated microtubules organised in a marginal band. During platelet activation, microtubules undergo major reorganisations, which contribute to the shape change of activating platelets. We show that, during these activation-induced shape changes, a dramatic HDAC6-mediated tubulin deacetylation takes place, followed by microtubule reacetylation in spread platelets. In addition, although HDAC6-controlled tubulin deacetylation is not required for platelet activation, the capacity of HDAC6 to prevent tubulin hyperacetylation influences the speed of platelet spreading. These results are particularly important in view of HDAC6 inhibitors being currently used in clinical trials and represent the first example of cell signalling by lysine acetylation in platelet biology.

  • Submitted May 9, 2012.
  • Accepted August 24, 2012.