Glycosylation in the control of selectin counter-receptor structure and function.
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.
Lowe
John B
JB
Howard Hughes Medical Institute, Department of Pathology, University of Michigan Medical School, Ann Arbor, 48109-0650, USA. JohnLowe@Umich.edu
D000954:Antigens, Surface / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D005544:Forecasting; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006031:Glycosylation; D006801:Humans; D019041:L-Selectin / Q000378:metabolism*; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D017351:N-Acetylglucosaminyltransferases / Q000737:chemistry / Q000378:metabolism
D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084882:P-selectin ligand protein; D019041:L-Selectin; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase