New insights of glycoprotein Ib-IX-V complex organization and glycoprotein Ibα in platelet biogenesis

Abstract

Purpose of review Glycoprotein (GP) Ib-IX-V, a platelet surface receptor that plays a critical role in platelet adhesion and platelet-mediated immune responses, consists of GPIbα, GPIbβ, GPIX, and GPV in a stoichiometry of 2 : 4 : 2 : 1. Forming a complex is essential for GPIb-IX-V to function. GPIb-IX-V also plays an important role in platelet biogenesis by regulating the number and size of platelets. Yet how GPIb-IX-V regulates platelet biogenesis remains elusive. This review will summarize recent findings in the complex organization of GPIb-IX-V and its role in platelet biogenesis. Recent findings Proteomics studies suggest that GPIbα, GPIbβ, GPIX, and GPV form the complex in a ratio of 1 : 2 : 1 : 1, which is supported by analysis of molecular weight of GPIb-IX-V and GPIb-IX and the structure of entire GPIb-IX-V. To activate platelets, GPIbα requires binding of CLEC-2 to trigger signals. Furthermore, disrupting the GPIbα anchorage to filamin A causes defects in platelet budding away from proplatelets leading to giant platelets and a low platelet count. Summary New studies challenge the traditional model for the organization of GPIb-IX-V as a complex and indicate the role of GPIb-IX-V in platelet production. Those studies provide insights for GPIb-IX-V in the regulation of platelet activation and platelet biogenesis.