title: Distinct glycosyltransferases synthesize E-selectin ligands in human vs. mouse leukocytes.
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.
authors.affiliation: Chemical and Biological Engineering and The NY State Center for Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY, USA.
authors.forename: Nandini
authors.initials: N
authors.lastname: Mondal
authors.forename: Alexander
authors.initials: A
authors.lastname: Buffone
authors.forename: Sriram
authors.initials: S
authors.lastname: Neelamegham
mesh_terms: D000818:Animals; D019040:E-Selectin / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*
chemical_list: D019040:E-Selectin; D005647:Fucosyltransferases
keywords: carbohydrate; cell adhesion; endothelial cell; fluid shear; fucosyltransferase; glycosyltransferase; inflammation; leukocyte; selectin; sialyl Lewis-X