Pathways regulating LIMK1 and cofilin in platelets (Paperback)

The activation of platelets is a central step during the physiological process of hemostasis and its understanding may lead us to control the pathophysiological process of intra-arterial thrombus formation and vascular occlusion, which can cause acute coronary syndrome and myocardial infarction. The morphological and functional changes of platelets require a drastic remodeling of the actin cytoskeleton regulated by numerous actin-binding proteins and signaling molecules such as the family of Rho-GTPases and associated kinases. Understanding of these signaling pathways is of priority to design anti-thrombotic drugs. This study explores the Rho-GTPases induced signaling mechanism during platelet activation by the physiological agonist thrombin and the pathophysiological relevant agonist lysophosphatidic acid (LPA), which is the main platelet-activating lipid in atherosclerotic plaque. It further elucidates the role of LIMK1 and cofilin phosphorylation during platelet activation and provides an explanation to how the phosphorylation of cofilin affects the actin dynamics underlying platelet activation. This work is intended for a better understanding of signaling in platelets.