Portal de Periódicos da CAPES

Interaction between Platelet Glycoprotein Ibα and Filamin-1 Is Essential for Glycoprotein Ib/IX Receptor Anchorage at High Shear

2002; Elsevier BV; Volume: 277; Issue: 3 Linguagem: Inglês

10.1074/jbc.m109384200

1083-351X

David M. Williamson, Inna Pikovski, Susan L. Cranmer, P Mangin, Nayna Mistry, Teresa Domagała, S. Chehab, François Lanza, Hatem H. Salem, Shaun P. Jackson,

Heparin-Induced Thrombocytopenia and Thrombosis

The interaction of the glycoprotein (GP) Ib-V-IX receptor complex with the membrane skeleton of platelets is dependent on a specific interaction between the cytoplasmic tail of GPIbα and filamin-1. This interaction has been proposed to regulate key aspects of platelet function, including the ligand binding of GPIb-V-IX and the ability of the cells to sustain adhesion to von Willebrand factor (vWf) under high shear. In this study we have examined sequences in the GPIbα intracellular domain necessary for interaction of the receptor with filamin-1. We have identified two adjacent sequences involving amino acids 557–568 and 569–579 of the GPIbα cytoplasmic domain that are critical for normal association between the receptor complex and filamin-1. Under flow conditions, Chinese hamster ovary (CHO) cells expressing these two mutant receptors exhibited an increase in translocation velocity that was associated with increased cell detachment from the vWf matrix at high shear. The shear-dependent acceleration in velocity of mutant Δ557–568 and Δ569–579 CHO cells was associated with a critical defect in receptor anchorage, evident from significant extraction of GPIb-IX from the CHO cell membrane at high shear. These studies define a critical role for amino acids within the 557–579 sequence of GPIbα for interaction with filamin-1.