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J. Biol. Chem., Vol. 281, Issue 32, 23050-23059, August 11, 2006

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The Transmembrane Domain of Glycoprotein Ib Is Critical to Efficient Expression of Glycoprotein Ib-IX Complex in the Plasma Membrane^*

Xi Mo, Nan Lu, Arnoldo Padilla, José A. López, and Renhao Li¹

From the Center for Membrane Biology, Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030 and the Thrombosis Research Section, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030

Lack of expression of glycoprotein (GP) Ib-IX-V complex in platelets often results from mutations in its three subunits: GP Ib, GP Ib, or GP IX. The requirement of all three subunits in the efficient surface expression of the receptor complex has been reproduced in Chinese hamster ovary cells. Here, we probed the role of the transmembrane domains in expression of the GP Ib-IX complex and potential interactions between these domains. Replacing the transmembrane domains of either GP Ib or GP Ib, but not that of GP IX, with unrelated sequences markedly diminished surface expression of the GP Ib-IX complex in transiently transfected Chinese hamster ovary cells. Replacement of the Ib transmembrane domain produced the largest effect. Furthermore, several single-site mutations in the Ib transmembrane domain were found to significantly decrease overall expression as well as surface expression of GP Ib, probably by perturbing the interaction between the Ib and Ib transmembrane domains and in turn reducing the stability of GP Ib in the cell. Mutations S503V and S503L in the Ib transmembrane domain partly reversed the expression-decreasing effect of mutation H139L, but not the others, in the Ib transmembrane domain, suggesting a specific interaction between these two polar residues. Together, our results have demonstrated the importance of the Ib transmembrane domain, through its interaction with the Ib counterpart, to the proper assembly and efficient surface expression of the GP Ib-IX complex.

Received for publication, January 30, 2006 , and in revised form, May 15, 2006.

^* This work was supported by American Heart Association, Texas Affiliate, Grant 0565078Y and National Institutes of Health Grant HL082808. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported in part by NCI, National Institutes of Health, Howard Temin Award CA096706. To whom correspondence should be addressed: Center for Membrane Biology, University of Texas Medical School, MSB 6.130, 6431 Fannin St., Houston, TX 77030. Tel.: 713-500-7233; Fax: 713-500-0545; E-mail: Renhao.Li{at}uth.tmc.edu.

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