title: Interaction of platelet endothelial cell adhesion molecule (PECAM) with α2,6-sialylated glycan regulates its cell surface residency and anti-apoptotic role.
abstract: The luminal sides of vascular endothelial cells are heavily covered with a so-called glycocalyx, but the precise role of the endothelial glycocalyx remains unclear. Our previous study showed that N-glycan α2,6-sialylation regulates the cell surface residency of an anti-apoptotic molecule, platelet endothelial cell adhesion molecule (PECAM), as well as the sensitivity of endothelial cells toward apoptotic stimuli. As PECAM itself was shown to be modified with biantennary N-glycans having α2,6-sialic acid, we expected that PECAM would possess lectin-like activity toward α2,6-sialic acid to ensure its homophilic interaction. To verify this, a series of oligosaccharides were initially added to observe their inhibitory effects on the homophilic PECAM interaction in vitro. We found that a longer α2,6-sialylated oligosaccharide exhibited strong inhibitory activity. Furthermore, we found that a cluster-type α2,6-sialyl N-glycan probe specifically bound to PECAM-immobilized beads. Moreover, the addition of the α2,6-sialylated oligosaccharide to endothelial cells enhanced the internalization of PECAM as well as the sensitivity to apoptotic stimuli. Collectively, these findings suggest that PECAM is a sialic acid binding lectin and that this binding property supports endothelial cell survival. Notably, our findings that α2,6-sialylated glycans influenced the susceptibility to endothelial cell apoptosis shed light on the possibility of using a glycan-based method to modulate angiogenesis.
authors.affiliation: From the Disease Glycomics Team and shinobuk@riken.jp.
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: From the Disease Glycomics Team and.
authors.forename: Rie
authors.initials: R
authors.lastname: Imamaki
authors.affiliation: From the Disease Glycomics Team and.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kurimoto
authors.affiliation: From the Disease Glycomics Team and.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Structural Glycobiology Team, RIKEN-Max Planck Joint Research Center, Global Research Cluster, and.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.affiliation: Structural Glycobiology Team, RIKEN-Max Planck Joint Research Center, Global Research Cluster, and.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, Saitama 351-0198, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Ishida
authors.affiliation: Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193, Japan, Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan, and.
authors.forename: Hiromune
authors.initials: H
authors.lastname: Ando
authors.affiliation: Department of Applied Bioorganic Chemistry, Gifu University, Gifu 501-1193, Japan, Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan, and.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kiso
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Hashii
authors.affiliation: Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Kawasaki
authors.affiliation: From the Disease Glycomics Team and.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D019276:Glycocalyx / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D037102:Lectins; D009844:Oligosaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011134:Polysaccharides; D019158:N-Acetylneuraminic Acid
keywords: Apoptosis; Cell Adhesion; Endothelial Cell; Lectin; Sialic Acid