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 α2–3sialylated, α1-3ucosylated 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 α1-3fucosyltransferases 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71944/1/j.1600-065X.2002.18603.x.pd