Structure and Function of the Proteasome System in Platelets

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Proteasome complexes are indispensable for the maintenance of protein homeostasis and the functional preservation of mammalian cells. Recently, we have shown that all catalytically active subunits of the standard and immunoproteasome are expressed in platelets. The main focus of the proposed research project is the investigation of the composition and function of the proteasome system in platelets. In detail, in the first and second part of the work programme the proteasome conformation under steady state conditions and after exposure of platelets to infectious agents shall be analyzed as well as the role of the activity of different proteasome isoforms on platelet activation and aggregation. In the third part of the work programme we will concentrate on answering the question whether platelet proteasomes are able to efficiently process and generate MHC class I bound epitopes. In case platelets generate MHC class I ligands at significant amounts their impact as immunomodulatory cells not only in the innate but also in the adaptive immune response will be emphasized. As consequence, platelets could be important players in the control of infections and should be considered as part of the immune system.