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J Thromb Haemost. 2012 Sep;10(9):1875-86. doi: 10.1111/j.1538-7836.2012.04841.x.

Transmembrane domains are critical to the interaction between platelet glycoprotein V and glycoprotein Ib-IX complex.

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1
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

BACKGROUND:

The glycoprotein (GP) Ib-IX-V complex, the von Willebrand factor receptor on the platelet surface, is critically involved in hemostasis and thrombosis. The GPV subunit interacts with GPIb-IX to form the GPIb-IX-V complex, but the underlying molecular basis remains unclear. It was observed earlier that efficient expression of GPV in the plasma membrane requires co-expression of GPIb-IX.

OBJECTIVES AND METHODS:

Hypothesizing that GPIb-IX stabilizes GPV through direct interaction and consequently enhances GPV surface expression, we aim in this study to identify structural elements in the complex that mediate the interaction between GPV and GPIb-IX by analyzing mutational effects on GPV surface expression in transfected Chinese hamster ovary cells.

RESULTS:

Enhancement of GPV surface expression by GPIb-IX requires transmembrane domains of both GPV and GPIbα, as replacing the GPV transmembrane domain with an unrelated poly-leucine-alanine sequence abolished the enhancing effect of GPIb-IX. Additional mutagenesis analysis of the GPV transmembrane helix identified three helical sides containing conserved polar residues as critical to efficient GPV surface expression. Similarly, replacing residues in three sides (Gly495/Ala502/Leu509, Phe491/Trp498/Val505, and Y492/L499/L506) of the GPIbα transmembrane domain with leucines preserved the surface expression level of GPIb-IX but significantly altered that of GPV.

CONCLUSIONS:

Our results demonstrate for the first time the importance of transmembrane domains for efficient surface expression of GPV and suggest that GPV and GPIbα transmembrane domains interact with each other, contributing to assembly of the GPIb-IX-V complex.

PMID:
22759073
PMCID:
PMC3499136
DOI:
10.1111/j.1538-7836.2012.04841.x
[Indexed for MEDLINE]
Free PMC Article
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