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

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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.