title: Characterization of the platelet granule proteome: evidence of the presence of MHC1 in alpha-granules.
abstract: In the present study, we performed an extensive qualitative characterization of the platelet granule proteome using subcellular fractionation followed by mass spectrometry analysis and functional annotation. Eight-hundred-and-twenty-seven proteins were identified, most of them being associated to granules and to the granule's secretory machinery. Functional pathway analysis revealed 30 pathways, including the major histocompatibility complex class 1 (MHC I) presenting antigen pathway. This pathway was of particular interest for its potential interrelation between platelets and the immune system. Key proteins belonging to this metabolic route such as β-2-microglobulin, 26S protease regulatory subunit 10B from the proteasome and proteins 1 and 2 of the transporter associated with antigen processing were shown to co-localize with von Willebrand factor in resting platelets and to be located on the plasma membrane when platelets were activated. Key proteins of the MHC1 antigen-presenting pathway are located in platelet alpha-granules. These results suggest a possible functional role of platelet granules in platelet-related immune modulation.
  
  
  CONCLUSIONS
  In this study, we described the largest dataset related to platelet granule proteins. We performed a functional pathway analysis that evidenced several expected granule-related pathways. We also highlighted the "Antigen processing and presentation" pathway that has drawn our attention. Using immunofluorescence technique, we confirmed the presence of several key proteins for antigen presentation in platelet granules. This study suggests a putative functional role of MHC1 and platelet granules in the immune modulation.
authors.affiliation: Division of Angiology and Haemostasis, Department of Medical Specialisations, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland; Biomedical Proteomics Research Group, Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Zufferey
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Domitille
authors.initials: D
authors.lastname: Schvartz
authors.affiliation: Division of Angiology and Haemostasis, Department of Medical Specialisations, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland; Biomedical Proteomics Research Group, Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Séverine
authors.initials: S
authors.lastname: Nolli
authors.affiliation: Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Division of Internal Medicine, and Rehabilitation, Trois-Chêne Hospital, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Reny
authors.affiliation: Biomedical Proteomics Research Group, Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Sanchez
authors.affiliation: Division of Angiology and Haemostasis, Department of Medical Specialisations, Faculty of Medicine and University Hospitals of Geneva, Geneva, Switzerland; Biomedical Proteomics Research Group, Department of Human Protein Sciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Platelet Group, Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: pierre.fontana@hcuge.ch.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontana
mesh_terms: D000328:Adult; D017951:Antigen Presentation; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure*; D001798:Blood Proteins / Q000032:analysis* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001798:Blood Proteins; D015395:Histocompatibility Antigens Class I; D020543:Proteome
keywords: Granules; MHC I; Platelet; Proteomics; β-2-Microglobulin