title: HDAC6 controls the kinetics of platelet activation.
abstract: HDAC6, a major cytoplasmic deacetylase, is shown here to fine-tune the kinetics of platelet activation, a process that must be precisely regulated to ensure hemostasis after blood vessel injury while preventing pathologic thrombus formation. The discoid shape of resting platelets in the circulation is maintained by several highly acetylated microtubules organized in a marginal band. During platelet activation, microtubules undergo major reorganizations, 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 signaling by lysine acetylation in platelet biology.
authors.affiliation: Inserm U823, Université Joseph Fourier, Grenoble 1, Institut Albert Bonniot, F-38700 Grenoble, France. karin.sadoul@ujf-grenoble.fr
authors.forename: Karin
authors.initials: K
authors.lastname: Sadoul
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Boubou
authors.initials: B
authors.lastname: Diagouraga
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Vitte
authors.forename: Thierry
authors.initials: T
authors.lastname: Buchou
authors.forename: Thérèse
authors.initials: T
authors.lastname: Rossini
authors.forename: Benoît
authors.initials: B
authors.lastname: Polack
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xi
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthias
authors.forename: Saadi
authors.initials: S
authors.lastname: Khochbin
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D048430:Cell Shape; D048429:Cell Size; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D000073864:Histone Deacetylase 6; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006655:Histone Deacetylases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008969:Molecular Sequence Data; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D014404:Tubulin / Q000378:metabolism
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D014404:Tubulin; C012589:trichostatin A; C433811:HDAC6 protein, human; C499033:Hdac6 protein, mouse; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases