Glycosylation in the Control of Selectin Counter-Receptor Structure and Function

Immunol Rev. 2002 Aug;186:19-36. doi: 10.1034/j.1600-065x.2002.18603.x.

Abstract

Leukocyte trafficking is characterized by sequential cell adhesion and activation events that deliver specific leukocyte subsets to distinct extravascular locations under different pathophysiological circumstances. E-, P- and/or L-selectin-dependent leukocyte-endothelial cell adhesive interactions contribute essentially to this process. Selectin counter-receptor activity on leukocyte and high endothelial venules is borne by specific glycoproteins whose ability to support adhesion requires specific post-translational modifications. These modifications are typified by serine/threonine-linked oligosaccharides capped with the sialyl Lewis x moiety, an alpha2-3sialylated, alpha1-3ucosylated tetrasaccharide synthesized by specific glycosyltransferases. Recent advances in glycan structure analysis and in characterizing mice with targeted deletions of glycosyltransferase and sulfotransferase genes discloses an essential role for 6-O GlcNAc sulfate modification of the sialyl Lewis x tetrasaccharide in L-selectin counter-receptor activity. Related studies identify novel extended Core 1 type O-glycans bearing the 6-sulfosialyl Lewis x moiety, define the molecular nature of the MECA-79 epitope, and disclose a requirement for the alpha1-3fucosyltransferases FucT-IV and FucT-VII in the elaboration of L-selectin counter-receptor activities. Parallel studies also demonstrate that these 2 fucosyltransferases, a core 2 GlcNAc transferase, and core 2-type sialyl Lewis x determinants make essential contributions to leukocyte P-selectin counter-receptor activity, and figure prominently in the control of leukocyte E-selectin counter-receptor activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antigens, Surface / chemistry
  • Antigens, Surface / metabolism
  • Antigens, Surface / physiology*
  • Forecasting
  • Fucosyltransferases / genetics
  • Fucosyltransferases / metabolism
  • Fucosyltransferases / physiology
  • Glycosylation
  • Humans
  • L-Selectin / metabolism*
  • Leukocyte Count
  • Leukocytes / immunology
  • Lymphocytes / immunology*
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins
  • N-Acetylglucosaminyltransferases / chemistry
  • N-Acetylglucosaminyltransferases / metabolism

Substances

  • Antigens, Surface
  • L-selectin counter-receptors
  • Membrane Glycoproteins
  • Membrane Proteins
  • P-selectin ligand protein
  • L-Selectin
  • Fucosyltransferases
  • N-Acetylglucosaminyltransferases
  • UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase