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HDAC6 controls the kinetics of platelet activation. | LitMetric

AI Article Synopsis

  • HDAC6 plays a crucial role in regulating platelet activation, which is essential for stopping bleeding while avoiding unwanted blood clots.
  • * The shape of resting platelets is maintained by acetylated microtubules, and during activation, HDAC6 facilitates the deacetylation of tubulin, which allows for significant shape changes.
  • * Although deacetylation by HDAC6 isn't necessary for activating platelets, it affects how quickly platelets spread, highlighting new insights into cell signaling related to acetylation in platelet function.

Article 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.

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Source
http://dx.doi.org/10.1182/blood-2012-05-428011DOI Listing

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