title: Lysine acetyltransfer supports platelet function.
abstract: OBJECTIVE
  The reversible acetylation of protein lysine ε-amino groups, catalyzed by lysine acetyltransferases and deacetylases, serves as a molecular switch in the orchestration of diverse cellular activities. Here, we aimed to investigate the role of lysine acetyltransfer in platelet function.
  
  
  RESULTS
  Proteomics methods identified 552 acetyllysine (acK) modifications on 273 platelet proteins that serve as candidate substrates for lysine acetyltransferases. Bioinformatics analyses of the identified acK-modified platelet proteins supported roles for the lysine acetyltransferase p300 in the regulation of actin-mediated platelet processes. Biochemical experiments showed that platelets express p300, which is activated in an Src kinase-dependent manner upon platelet stimulation with the platelet glycoprotein VI agonist collagen-related peptide (CRP). Inhibition of platelet p300 abrogated CRP-stimulated lysine acetylation of actin, filamin, and cortactin, as well as F-actin polymerization, integrin activation, and platelet aggregation. Super-resolution visualization of platelet actin-rich adhesion structures revealed abundant acK protein colocalized with platelet actin cytoskeletal proteins. Inhibition of p300 blocked platelet filopodium formation and the spreading of platelets on fibrinogen and collagen surfaces. In whole blood, p300 inhibition prevented the formation of platelet aggregates under shear, suggesting a physiologic role for lysine acetyltransferase activity in platelet function.
  
  
  CONCLUSIONS
  Together, our findings reveal lysine acetyltransfer to be a potential regulator of platelet actin dynamics, and potential roles for lysine acetylation in the molecular coordination of platelet activation and function.
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.|Cell and Developmental Biology, Portland, OR, USA.|Knight Cardiovascular Institute, Portland, OR, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Aslan
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Rigg
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.|Department of Medical Physics, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq, France.
authors.forename: M S
authors.initials: MS
authors.lastname: Nowak
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.
authors.forename: C P
authors.initials: CP
authors.lastname: Loren
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Baker-Groberg
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.
authors.forename: J
authors.initials: J
authors.lastname: Pang
authors.affiliation: Proteomics Shared Resource, Oregon Health & Science University, Portland, OR, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: David
authors.affiliation: Department of Biomedical Engineering, Portland, OR, USA.|Cell and Developmental Biology, Portland, OR, USA.|Division of Hematology & Medical Oncology School of Medicine, Portland, OR, USA.
authors.forename: O J T
authors.initials: OJ
authors.lastname: McCarty
mesh_terms: D000107:Acetylation; D008841:Actin Cytoskeleton / Q000201:enzymology; D000199:Actins / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D001798:Blood Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D048430:Cell Shape; D019295:Computational Biology; D004789:Enzyme Activation; D006801:Humans; D008239:Lysine; D010455:Peptides / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D050880:p300-CBP Transcription Factors / Q000097:blood*; D019061:src-Family Kinases / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
chemical_list: D000199:Actins; D001798:Blood Proteins; D002352:Carrier Proteins; D008239:Lysine; D010455:Peptides; D050880:p300-CBP Transcription Factors; D019061:src-Family Kinases; D000099224:p300-CBP-Associated Factor; C435908:collagen-related peptide
keywords: acetyltransferases; actin; metabolism; p300 acetyltransferase; platelets