Differential requirements for the O-linked branching enzyme core 2 β1-6-N-glucosaminyltransferase in biosynthesis of ligands for E-selectin and P-selectin

Karen R. Snapp, Christine E. Heitzig, Lesley G. Ellies, Jamey D. Marth, Geoffrey S. Kansas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

Selectins are carbohydrate-binding adhesion molecules that play important roles in control of leukocyte traffic. Glycosyltransferases involved in selectin ligand biosynthesis include the α1,3-fucosyltransferases FucT-VII and FucT-IV, one or more sialyltransferases, and at least one O-linked branching enzyme. Previous studies have shown that core 2 β1-6-N-glucosaminyltransferase (C2GIcNAcT-I; EC 2.4.1.102) is required for functional modification of PSGL-1, the leukocyte P-selectin ligand, but have been ambiguous on whether this enzyme is involved in E-selectin ligand formation. Using an attachment and rolling assay under defined shear flow in vitro, this study shows that C2GIcNAcT-I- lymphoid cells stably transfected with FucT-VII complementary DNA attach and roll well on E-selectin at 1.5 dynes/cm.2 Further, attachment and rolling on P-selectin of neutrophils is sharply reduced and that of short-term polarized Th1 cells is virtually abolished, with leukocytes from C2GIcNAcT-I-/- mice. In contrast, both neutrophils and Th1 cells from C2GIcNAcT-I-/- mice attach and roll as well as wild-type cells on E-selectin. These results show that C2GIcNAcT-I is selectively required for biosynthesis of ligands for P-selectin, but is not essential for at least some E-selectin ligands. Distinct requirements for C2GIcNAcT-I in the formation of ligands for E-selectin versus P-selectin represents a novel level of regulation of expression of selectin ligands and lymphocyte traffic.

Original languageEnglish (US)
Pages (from-to)3806-3811
Number of pages6
JournalBlood
Volume97
Issue number12
DOIs
StatePublished - Jun 15 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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