Structure and Function of the Proteasome System in Platelets

蛋白酶体复合物对于维持蛋白质稳态和哺乳动物细胞的功能保护是不可或缺的。最近，我们已经表明，所有的催化活性亚基的标准和免疫蛋白酶体中表达的血小板。拟议研究项目的主要重点是研究血小板中蛋白酶体系统的组成和功能。具体而言，在工作计划的第一和第二部分中，应分析稳态条件下和血小板暴露于感染因子后的蛋白酶体构象，以及不同蛋白酶体亚型的活性对血小板活化和聚集的作用。在工作计划的第三部分中，我们将集中回答血小板蛋白酶体是否能够有效地加工和产生MHC I类结合表位的问题。在血小板产生大量MHC I类配体的情况下，将强调它们作为免疫调节细胞不仅在先天免疫应答中而且在适应性免疫应答中的影响。因此，血小板可能是控制感染的重要参与者，应被视为免疫系统的一部分。

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.