O-glycans direct selectin ligands to lipid rafts on leukocytes

摘要: Palmitoylated cysteines typically target transmembrane proteins to domains enriched in cholesterol and sphingolipids (lipid rafts). P-selectin glycoprotein ligand-1 (PSGL-1), CD43, CD44 are O-glycosylated on leukocytes that associate with lipid rafts. During inflammation, they transduce signals by engaging selectins as roll venules, move the raft-enriched uropods of polarized cells upon chemokine stimulation. It is not known how these glycoproteins rafts or whether this association required for signaling translocation uropods. Here, we found loss core 1-derived O-glycans murine C1galt1−/− neutrophils blocked raft targeting PSGL-1, CD44, but other glycosylated proteins, measured resistance solubilization nonionic detergent copatching a raft-resident sphingolipid intact cells. Neuraminidase removal sialic acids from wild-type also targeting. neuraminidase-treated failed activate tyrosine kinases when plated immobilized anti–PSGL-1 anti-CD44 F(ab′)2. Furthermore, incubated F(ab′)2 did generate microparticles. In marked contrast, moved normally chemokine-stimulated neutrophils. These data define role terminal ligands leukocytes. Preassociation movement