Abstract Number: PB1828
Meeting: ISTH 2020 Congress
Background: The proteasome and especially the immunoproteasome with its increased catalytic activity are major proteolytic components contributing to immune cell functions by generating the peptides essential for MHC class I presentation. Platelets express active proteasome complexes that are responsible for protein degradation and regulation of signal transduction processes. However the actual role of the proteasome in platelets remains unclear.
Aims: Characterization of the proteasome and antigen processing and presentation pathway (APP) machinery of platelets
Methods: We identified the catalytically active standard and immunoproteasome subunits as well as APP components in freshly isolated platelets as well as in stored platelets by immunoblot. Proteasome components were purified from washed platelets and their proteasomal activity was determined by fluorogenic peptide substrates. Protein synthesis in stored platelets was inhibited by puromycin treatment.
Results: We identified both, the catalytically active standard proteasome subunits β1/delta, β2/Z and β5/MB1 and immunoproteasome subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 in platelets of >10 healthy donors (Fig 1A, B). For these subunits we observed chymotrypsin-like, caspase-like and trypsin-like proteasome activity, respectively in freshly prepared platelets, which was maintained during 7 days of storage, even when protein synthesis was inhibited. We identified the expression of all APP components required for successful MHC class I presentation (Fig. 1C, D).
Conclusions: The standard proteasome and immunoproteasome are fully functional in platelets. In contrast to other immune cells, the platelet proteasome has a 20 times longer halflife. The high stability of the platelet proteasome might foster platelet functions in hemostasis and immune response by modulation of proteins involved in signaling or MHC class I antigen presentation.
To cite this abstract in AMA style:Colberg L, Wesche J, Cammann C, Seifert U, Greinacher A. Platelets Express a Stable and Functional Proteasome System and All Components of the Antigen Processing and Presentation Pathway (APP) Machinery [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelets-express-a-stable-and-functional-proteasome-system-and-all-components-of-the-antigen-processing-and-presentation-pathway-app-machinery/. Accessed January 26, 2022.
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