The Journal of Experimental Medicine
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Published online 14 October 2002 doi:10.1084/jem.20020143
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© Rockefeller University Press, 0022-1007/2002/10/1057 $5.00
The Journal of Experimental Medicine, Volume 196, Number 8, 1057-1066

Localization of the Adhesion Receptor Glycoprotein Ib-IX-V Complex to Lipid Rafts Is Required for Platelet Adhesion and Activation

Corie N. Shrimpton, Gautam Borthakur, Susana Larrucea, Miguel A. Cruz, Jing-Fei Dong and José A. López

Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, TX 77030

Address correspondence to J. López, Thrombosis Research Section, Dept. of Medicine, BCM 286, N1319, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: 713-798-3470; Fax: 713-798-3415; E-mail: josel{at}bcm.tmc.edu

The platelet glycoprotein (GP) Ib-IX-V complex mediates the attachment of platelets to the blood vessel wall by binding von Willebrand factor (VWF), an interaction that also transmits signals for platelet activation and aggregation. Because the complex is extensively palmitoylated, a modification known to target proteins to lipid rafts, we investigated the role of raft localization in GP Ib-IX-V functions. In unstimulated platelets, a minor portion of the complex localized to Triton-insoluble raft fractions; this portion increased three to sixfold with platelet activation by VWF. Raft-associated GP Ib-IX-V was selectively palmitoylated, with GP Ib-IX-V–associated palmitate increasing in the raft fraction on VWF-mediated activation. The raft fraction was also the site of association between GP Ib-IX-V and the Fc receptor Fc{gamma}RIIA. The importance of this association was demonstrated by the ability of the Fc{gamma}RIIA antibody IV.3 to inhibit shear-induced platelet aggregation. Disruption of rafts by depleting membrane cholesterol impaired several GP Ib-IX-V–dependent platelet fractions: aggregation to VWF under static conditions and under shear stress, tyrosine phosphorylation, and adhesion to a VWF surface. Partial restoration of membrane cholesterol content partially restored shear-induced platelet aggregation and tyrosine phosphorylation. Thus, localization of the GP Ib-IX-V complex within rafts is crucial for both platelet adhesion and postadhesion signaling.

Key Words: platelets • membrane microdomains • von Willebrand factor • cholesterol • signaling


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