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Lysine acetyltransfer supports platelet function.

J E Aslan1,2,3, R A Rigg1, M S Nowak1,4

  • 1Department of Biomedical Engineering, Portland, OR, USA.

Journal of Thrombosis and Haemostasis : JTH
|August 11, 2015
PubMed
Summary
This summary is machine-generated.

Lysine acetyltransfer regulates platelet function by modifying actin dynamics. Inhibition of lysine acetyltransferase p300 impaired platelet activation, aggregation, and filopodium formation, highlighting its role in platelet processes.

Keywords:
acetyltransferasesactinmetabolismp300 acetyltransferaseplatelets

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Hematology

Background:

  • Protein lysine acetylation is a reversible post-translational modification regulating cellular activities.
  • Lysine acetyltransferases (KATs) and deacetylases control acetylation levels.
  • The role of lysine acetylation in platelet function remained largely unexplored.

Purpose of the Study:

  • To investigate the role of lysine acetyltransfer in platelet function.
  • To identify substrates of KATs in platelets.
  • To elucidate the specific KAT involved and its mechanism of action in platelet activation.

Main Methods:

  • Proteomics to identify acetylated lysine (acK) modifications on platelet proteins.
  • Bioinformatics analysis to predict KAT substrates.
  • Biochemical assays to study p300 expression, activation, and function in platelets.
  • Inhibition studies using p300 inhibitors.
  • Super-resolution microscopy to visualize acK proteins and actin structures.
  • Whole blood assays to assess platelet aggregation under shear stress.

Main Results:

  • Identified 552 acK modifications on 273 platelet proteins.
  • Bioinformatics suggested a role for KAT p300 in actin-mediated platelet processes.
  • Platelets express p300, activated by collagen-related peptide (CRP) via Src kinase.
  • p300 inhibition reduced acetylation of actin, filamin, and cortactin, impairing F-actin polymerization, integrin activation, and platelet aggregation.
  • p300 inhibition blocked filopodium formation, platelet spreading, and aggregate formation under shear.

Conclusions:

  • Lysine acetyltransfer, particularly via p300, regulates platelet actin dynamics.
  • Lysine acetylation plays a crucial role in the molecular coordination of platelet activation and function.
  • These findings suggest potential therapeutic targets for modulating platelet activity.