The GPIb-IX complex on platelets: insight into its novel physiological functions affecting immune surveillance, hepatic thrombopoietin generation, platelet clearance and its relevance for cancer development and metastasis
Gerd Bendas, Martin Schlesinger
Abstract
The glycoprotein (GP) Ib-IX complex is a platelet receptor that mediates the initial interaction with subendothelial von Willebrand factor (VWF) causing platelet arrest at sites of vascular injury even under conditions of high shear. GPIb-IX dysfunction or deficiency is the reason for the rare but severe Bernard-Soulier syndrome (BSS), a congenital bleeding disorder. Although knowledge on GPIb-IX structure, its basic functions, ligands, and intracellular signaling cascades have been well established, several advances in GPIb-IX biology have been made in the recent years. Thus, two mechanosensitive domains and a trigger sequence in GPIb were characterized and its role as a thrombin receptor was deciphered. Furthermore, it became clear that GPIb-IX is involved in the regulation of platelet production, clearance and thrombopoietin secretion. GPIb is deemed to contribute to liver cancer development and metastasis. This review recapitulates these novel findings highlighting GPIb-IX in its multiple functions as a key for immune regulation, host defense, and liver cancer development.