Article: article d'un périodique ou d'un magazine.
P-selectin glycoprotein ligand-1 decameric repeats regulate selectin-dependent rolling under flow conditions.
Journal of Biological Chemistry
Date de publication
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
P-selectin glycoprotein ligand-1 (PSGL-1) interacts with selectins to support leukocyte rolling along vascular wall. L- and P-selectin bind to N-terminal tyrosine sulfate residues and to core-2 O-glycans attached to Thr-57, whereas tyrosine sulfation is not required for E-selectin binding. PSGL-1 extracellular domain contains decameric repeats, which extend L- and P-selectin binding sites far above the plasma membrane. We hypothesized that decamers may play a role in regulating PSGL-1 interactions with selectins. Chinese hamster ovary cells expressing wild-type PSGL-1 or PSGL-1 molecules exhibiting deletion or substitution of decamers with the tandem repeats of platelet glycoprotein Ibalpha were compared in their ability to roll on selectins and to bind soluble L- or P-selectin. Deletion of decamers abrogated soluble L-selectin binding and cell rolling on L-selectin, whereas their substitution partially reversed these diminutions. P-selectin-dependent interactions with PSGL-1 were less affected by decamer deletion. Videomicroscopy analysis showed that decamers are required to stabilize L-selectin-dependent rolling. Importantly, adhesion assays performed on recombinant decamers demonstrated that they directly bind to E-selectin and promote slow rolling. Our results indicate that the role of decamers is to extend PSGL-1 N terminus far above the cell surface to support and stabilize leukocyte rolling on L- or P-selectin. In addition, they function as a cell adhesion receptor, which supports approximately 80% of E-selectin-dependent rolling.
Animals, CHO Cells, Cell Adhesion, Cell Membrane/metabolism, Cricetinae, Cricetulus, Humans, K562 Cells, Leukocyte Rolling, Membrane Glycoproteins/metabolism, Membrane Glycoproteins/physiology, Microscopy, Video, Models, Biological, Protein Structure, Tertiary, Selectins/chemistry, Tyrosine/analogs & derivatives, Tyrosine/chemistry
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