Relevance and molecular mechanisms of zinc homeostasis in megakaryo-poiesis and platelet function (A09+)

尽管Zn2+代谢包括催化、调节和结构功能已受到广泛关注，但在包括巨核细胞和血小板在内的许多细胞类型中，控制细胞Zn2+稳态的分子机制仍不清楚。这个项目的目的是：(i)利用从血小板功能紊乱的人类患者以及正常或改变的Zn2+调节的小鼠模型分离的血小板，了解Zn2+稳态在止血和血栓炎性疾病中的重要性；（ii）确定细胞内的Zn2+储存在mk /血小板中；（iii）阐明Zn2+在细胞膜和细胞膜内转运的分子机制，以及它对血小板信号传导的影响。

Although Zn2+ metabolism including catalytic, regulatory and structural functions has received extensive attention, the molecular mechanisms that control cellular Zn2+ homeostasis remain poorly defined in many cell types including megakaryocytes and platelets. The aim of this pro-ject is (i) to understand the importance of Zn2+ homeostasis in haemostatic and thrombo-inflammatory diseases using platelets isolated from human patients with thrombocyte function disorders as well as mouse models with normal or altered Zn2+ regulation, (ii) to identify the in-tracellular Zn2+ stores in MKs/platelets and (iii) to elucidate the molecular mechanisms of Zn2+ transport across the plasma- and intracellular membranes as well as its consequence for plate-let signalling.