Studies on regulation and signaling of the platelet glycoproteins GPV and GPVI [Elektronische Ressource] / vorgelegt von Amrei Strehl

Studies on regulation and signaling of platelet glycoproteins GPV and GPVI Dissertation zur Erlangung des naturwissenschaftlichen Doktorgrades der Bayerischen Julius-Maximilians-Universität Würzburg vorgelegt von Amrei Strehl aus Dortmund Würzburg, Dezember 2006 Eingereicht am: Mitglieder der Promotionskommission: Vorsitzender: 1. Gutachter: Prof. Dr. G. Krohne 2. Dr. B. Nieswandt Tag des Promotionskolloquiums: Doktorurkunde ausgehändigt am: 2 Summary Summary Platelets are crucial to inhibit extensive blood loss at sites of vascular injury. However, under pathological conditions such as rupture of an atherosclerotic plaque, activated platelets form aggregates that may occlude the vessel. This can lead to heart attack and stroke. Various and complex signaling pathways in the cell are involved in the steps of platelet adhesion, activation and aggregation. Single aspects of these processes were studied in three different subprojects in this work. The Glycoprotein (GP) Ib-V-IX complex is responsible for the first contact of platelets with the vessel wall. Subsequently, GPVI can bind to collagen of the subendothelium, which initiates a signaling cascade leading to platelet activation, aggregation, characterized by integrin activation and granule secretion and platelet procoagulant activity.