Sialyl-Lewisx on P-Selectin Glycoprotein Ligand-1 Is Regulated during Differentiation and Maturation of Dendritic Cells: A Mechanism Involving the Glycosyltransferases C2GnT1 and ST3Gal I

Julien, Sylvain; Grimshaw, Matthew J.; Sutton-Smith, Mark; Coleman, Julia; Morris, Howard R.; Dell, Anne; Taylor‐Papadimitriou, Joyce; Burchell, Joy

doi:10.4049/jimmunol.179.9.5701

Cited by 42 publications

(52 citation statements)

References 53 publications

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“…It also revealed the existence of ␣(2,6) sialylated glycans including the mono-(Gal␤1,3(NeuAc␣2,6) GalNAc; m/z 895.1) and di-(NeuAc␣2,3Gal␤1,3 (NeuAc␣2,6)GalNAc, m/z 1256.3) sialylated T-antigens at this position. Although similar structures have been observed during whole cell O-glycome analysis of a variety of PSGL-1 bearing cells including monocytes, dendritic cells, and neutrophils (34,35), this is the first report of the expression of such glycans at the N terminus of PSGL-1.…”

Section: Glycan Microheterogeneity At the N Terminus Of Psgl-1-supporting

confidence: 76%

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Competition between Core-2 GlcNAc-transferase and ST6GalNAc-transferase Regulates the Synthesis of the Leukocyte Selectin Ligand on Human P-selectin Glycoprotein Ligand-1

Antonopoulos

Gupta

et al. 2013

Journal of Biological Chemistry

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Background: Carbohydrate epitopes at the N terminus of PSGL-1 (P-selectin glycoprotein ligand-1) facilitate leukocyte binding to selectins. Results: O-linked glycan microheterogeneity analysis at the PSGL-1 N terminus demonstrates the presence of both the core-2 sialyl Lewis-X (sLe X ) and di-sialylated T-antigen. Conclusion: Overexpression of ST6GalNAc-transferases reduced both sLe X expression and selectin-mediated leukocyte adhesion. Significance: ST6GalNAc2 is a novel enzyme that regulates leukocyte adhesion under fluid shear.

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Section: Glycan Microheterogeneity At the N Terminus Of Psgl-1-supporting

confidence: 76%

“…In the case of dendritic cells, maturation is accompanied by a decrease in C2GnT-1 and an increase in ST6GalNAc2 transcript levels (34). Based on the current work, a transition from the core-2 sLe X glycan to the di-sialylated T-antigen may be expected at the PSGL-1 N terminus.…”

Section: A Potential Role For St6galnac2 In Regulating Leukocytementioning

confidence: 55%

Competition between Core-2 GlcNAc-transferase and ST6GalNAc-transferase Regulates the Synthesis of the Leukocyte Selectin Ligand on Human P-selectin Glycoprotein Ligand-1

Antonopoulos

Gupta

et al. 2013

Journal of Biological Chemistry

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“…Recently, a genetic remodeling of glycosylation upon DC maturation was demonstrated by glyco-gene microarray expression analysis (6,7) and by quantitative RT-PCR (8,9). A number of transcripts for enzymes involved in N-glycan synthesis was found to be increased during DC differentiation but downregulated after their maturation (6-8, 10, 11).…”

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confidence: 99%

Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type N-Glycans

Schlickeiser

Stanojlović²,

Appelt

et al. 2011

The Journal of Immunology

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The activity of α-1,2-mannosidase I is required for the conversion of high-mannose to hybrid-type (ConA reactive) and complex-type N-glycans (Phaseolus vulgaris-leukoagglutinin [PHA-L] reactive) during posttranslational protein N-glycosylation. We recently demonstrated that α-1,2-mannosidase I mRNA decreases in graft-infiltrating CD11c+ dendritic cells (DCs) prior to allograft rejection. Although highly expressed in immature DCs, little is known about its role in DC functions. In this study, analysis of surface complex-type N-glycan expression by lectin staining revealed the existence of PHA-Llow and PHA-Lhigh subpopulations in murine splenic conventional DCs, as well as in bone marrow-derived DC (BMDCs), whereas plasmacytoid DCs are nearly exclusively PHA-Lhigh. Interestingly, all PHA-Lhigh DCs displayed a strongly reduced responsiveness to TNF-α–induced p38-MAPK activation compared with PHA-Llow DCs, indicating differences in PHA-L–binding capacities between DCs with different inflammatory properties. However, p38 phosphorylation levels were increased in BMDCs overexpressing α-1,2-mannosidase I mRNA. Moreover, hybrid-type, but not complex-type, N-glycans are required for TNF-α–induced p38-MAPK activation and subsequent phenotypic maturation of BMDCs (MHC-II, CD86, CCR7 upregulation). α-1,2-mannosidase I inhibitor-treated DCs displayed diminished transendothelial migration in response to CCL19, homing to regional lymph nodes, and priming of IFN-γ–producing T cells in vivo. In contrast, the activity of α-1,2-mannosidase I is dispensable for LPS-induced signaling, as well as the DCs’ general capability for phenotypic and functional maturation. Systemic application of an α-1,2-mannosidase I inhibitor was able to significantly prolong allograft survival in a murine high-responder corneal transplantation model, further highlighting the importance of N-glycan processing by α-1,2-mannosidase I for alloantigen presentation and T cell priming.

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“…Expression of core 2 structures has been shown to regulate monocyte extravasation and migration of monocyte-derived dendritic cells to lymph nodes (57)(58)(59). BoHV-4 could therefore regulate extravasation of infected monocytes and migration of these cells in tissues or toward draining lymph nodes by modulating glycan structures at the infected cell surface.…”

Section: Discussionmentioning

confidence: 99%

Bovine Herpesvirus 4 Modulates Its β-1,6- N -Acetylglucosaminyltransferase Activity through Alternative Splicing

Lété

Markine-Goriaynoff

Machiels

et al. 2016

J Virol

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Carbohydrates play major roles in host-virus interactions. It is therefore not surprising that, during coevolution with their hosts, viruses have developed sophisticated mechanisms to hijack for their profit different pathways of glycan synthesis. Thus, the Bo17 gene of Bovine herpesvirus 4 (BoHV-4) encodes a homologue of the cellular core 2 protein ␤-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M), which is a key player for the synthesis of complex O-glycans. Surprisingly, we show in this study that, as opposed to what is observed for the cellular enzyme, two different mRNAs are encoded by the Bo17 gene of all available BoHV-4 strains. While the first one corresponds to the entire coding sequence of the Bo17 gene, the second results from the splicing of a 138-bp intron encoding critical residues of the enzyme. Antibodies generated against the Bo17 C terminus showed that the two forms of Bo17 are expressed in BoHV-4 infected cells, but enzymatic assays revealed that the spliced form is not active. In order to reveal the function of these two forms, we then generated recombinant strains expressing only the long or the short form of Bo17. Although we did not highlight replication differences between these strains, glycomic analyses and lectin neutralization assays confirmed that the splicing of the Bo17 gene gives the potential to BoHV-4 to fine-tune the global level of core 2 branching activity in the infected cell. Altogether, these results suggest the existence of new mechanisms to regulate the activity of glycosyltransferases from the Golgi apparatus. IMPORTANCEViruses are masters of adaptation that hijack cellular pathways to allow their growth. Glycans play a central role in many biological processes, and several studies have highlighted mechanisms by which viruses can affect glycosylation. Glycan synthesis is a nontemplate process regulated by the availability of key glycosyltransferases. Interestingly, bovine herpesvirus 4 encodes one such enzyme which is a key enzyme for the synthesis of complex O-glycans. In this study, we show that, in contrast to cellular homologues, this virus has evolved to alternatively express two proteins from this gene. While the first one is enzymatically active, the second results from the alternative splicing of the region encoding the catalytic site of the enzyme. We postulate that this regulatory mechanism could allow the virus to modulate the synthesis of some particular glycans for function at the location and/or the moment of infection.

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Sialyl-Lewisx on P-Selectin Glycoprotein Ligand-1 Is Regulated during Differentiation and Maturation of Dendritic Cells: A Mechanism Involving the Glycosyltransferases C2GnT1 and ST3Gal I

Cited by 42 publications

References 53 publications

Competition between Core-2 GlcNAc-transferase and ST6GalNAc-transferase Regulates the Synthesis of the Leukocyte Selectin Ligand on Human P-selectin Glycoprotein Ligand-1

Competition between Core-2 GlcNAc-transferase and ST6GalNAc-transferase Regulates the Synthesis of the Leukocyte Selectin Ligand on Human P-selectin Glycoprotein Ligand-1

Control of TNF-Induced Dendritic Cell Maturation by Hybrid-Type N-Glycans

Bovine Herpesvirus 4 Modulates Its β-1,6- N -Acetylglucosaminyltransferase Activity through Alternative Splicing

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