Impaired signaling pathways in Glanzmann thrombasthenia platelets

Introduction Activation of platelets during primary hemostasis can induce various processes. Among others, reorganization of the actin cytoskeleton leads to platelet shape change. Preliminary work has shown that the GPIIb/IIIa complex plays a crucial role in this process. Platelets from Glanzmann thrombasthenia (GT) patients with a quantitative or qualitative defect of the GPIIb/IIIa complex were examined. It was found that the GT platelets persisted in an early form of spreading (large number of long pseudopodia) and showed a defect in lamellipodia formation. Therefore, the aim of this study was to investigate the signaling pathways of GT platelets with regard to cytoskeleton reorganization. Since platelets lack a nucleus, signaling pathways are often regulated by post-translational modifications. Here, phosphorylations in particular play a crucial role. Based on this, different signaling molecules downstream of the GPIIb/IIIa complex were investigated to identify possible pathway changes leading to the altered shape change. For this aim, a protein-protein network was first constructed in silico using PlateletWeb to identify important proteins of the GPIIb/IIIa signaling pathways, which were further investigated.