Distinct glycosyltransferases synthesize E-selectin ligands in human vs. mouse leukocytes

Nandini Mondal, Alexander Buffone, Sriram Neelamegham

Research output: Contribution to journalComment/debatepeer-review

19 Scopus citations

Abstract

The binding of selectins to carbohydrate epitopes expressed on leukocytes is the first step in a multi-step cell adhesion cascade that controls the rate of leukocyte recruitment at sites of inflammation. The glycans that function as selectin-ligands are post-translationally synthesized by the serial action of Golgi resident enzymes called glycosyltransferases (glycoTs). Whereas much of our current knowledge regarding the role of glycoTs in constructing selectin-ligands comes from reconstituted biochemical investigations or murine models, tools to assess the impact of these enzymes on the human ligands are relatively underdeveloped. This is significant since the selectin-ligands, particularly those that bind E-selectin, vary between different leukocyte cell populations and they are also different in humans compared with mice. To address this shortcoming, a recent study by Buffone et al. (2013) outlines a systematic strategy to knockdown upto three glycoTs simultaneously in human leukocytes. The results suggest that the fucosyltransferases (FUTs) regulating selectin-ligand synthesis may be species-specific. In particular, they demonstrate that FUT9 plays a significant role during human, but not mouse, leukocyte-endothelial interactions. Overall, this article discusses the relative roles of the FUTs during human L-, E- and P-selectin-ligand biosynthesis, and the potential that the knockdown strategy outlined here may assess the role of other glycoTs in human leukocytes also.

Original languageEnglish (US)
Pages (from-to)288-292
Number of pages5
JournalCell Adhesion and Migration
Volume7
Issue number3
DOIs
StatePublished - 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Keywords

  • Carbohydrate
  • Cell adhesion
  • Endothelial cell
  • Fluid shear
  • Fucosyltransferase
  • Glycosyltransferase
  • Inflammation
  • Leukocyte
  • Selectin
  • Sialyl Lewis-X

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