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5. Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis

Author

Kawahara, Rebeca, Chernykh, Anastasia, Alagesan, Kathirvel, Bern, Marshall, Cao, Weiqian, Chalkley, Robert J, Cheng, Kai, Choo, Matthew S, Edwards, Nathan, Goldman, Radoslav, Hoffmann, Marcus, Hu, Yingwei, Huang, Yifan, Kim, Jin Young, Kletter, Doron, Liquet, Benoit, Liu, Mingqi, Mechref, Yehia, Meng, Bo, Neelamegham, Sriram, Nguyen-Khuong, Terry, Nilsson, Jonas, Pap, Adam, Park, Gun Wook, Parker, Benjamin L, Pegg, Cassandra L, Penninger, Josef M, Phung, Toan K, Pioch, Markus, Rapp, Erdmann, Sakalli, Enes, Sanda, Miloslav, Schulz, Benjamin L, Scott, Nichollas E, Sofronov, Georgy, Stadlmann, Johannes, Vakhrushev, Sergey Y, Woo, Christina M, Wu, Hung-Yi, Yang, Pengyuan, Ying, Wantao, Zhang, Hui, Zhang, Yong, Zhao, Jingfu, Zaia, Joseph, Haslam, Stuart M, Palmisano, Giuseppe, Yoo, Jong Shin, Larson, Göran, Khoo, Kai-Hooi, Medzihradszky, Katalin F, Kolarich, Daniel, Packer, Nicolle H, and Thaysen-Andersen, Morten

Subjects
Glycopeptides, Glycoproteins, Glycosylation, Humans, Informatics, Proteome, Proteomics, Research Personnel, Software, Tandem Mass Spectrometry, Biological Sciences, Technology, Medical and Health Sciences, Developmental Biology
Abstract

Glycoproteomics is a powerful yet analytically challenging research tool. Software packages aiding the interpretation of complex glycopeptide tandem mass spectra have appeared, but their relative performance remains untested. Conducted through the HUPO Human Glycoproteomics Initiative, this community study, comprising both developers and users of glycoproteomics software, evaluates solutions for system-wide glycopeptide analysis. The same mass spectrometrybased glycoproteomics datasets from human serum were shared with participants and the relative team performance for N- and O-glycopeptide data analysis was comprehensively established by orthogonal performance tests. Although the results were variable, several high-performance glycoproteomics informatics strategies were identified. Deep analysis of the data revealed key performance-associated search parameters and led to recommendations for improved 'high-coverage' and 'high-accuracy' glycoproteomics search solutions. This study concludes that diverse software packages for comprehensive glycopeptide data analysis exist, points to several high-performance search strategies and specifies key variables that will guide future software developments and assist informatics decision-making in glycoproteomics.

Published
2021

8. Hypoxia Controls the Glycome Signature and Galectin-8–Ligand Axis to Promote Protumorigenic Properties of Metastatic Melanoma

Author

Chakraborty, Asmi, Perez, Mariana, Carroll, Jordan D., Antonopoulos, Aristotelis, Dell, Anne, Ortega, Liettel, Mohammed, Norhan B.B., Wells, Michael, Staudinger, Caleb, Griswold, Anthony, Chandler, Kevin B., Marrero, Cristina, Jimenez, Ramon, Tani, Yoshihiko, Wilmott, James S., Thompson, John F., Wang, Wei, Sackstein, Robert, Scolyer, Richard A., Murphy, George F., Haslam, Stuart M., and Dimitroff, Charles J.

Published
2023
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10. XBP1s activation can globally remodel N-glycan structure distribution patterns

Author

Wong, Madeline Y, Chen, Kenny, Antonopoulos, Aristotelis, Kasper, Brian T, Dewal, Mahender B, Taylor, Rebecca J, Whittaker, Charles A, Hein, Pyae P, Dell, Anne, Genereux, Joseph C, Haslam, Stuart M, Mahal, Lara K, and Shoulders, Matthew D

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Underpinning research, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, Aetiology, Generic health relevance, Cell Line, Cell Line, Tumor, HEK293 Cells, HeLa Cells, Humans, Mannose, Polysaccharides, Proteome, Signal Transduction, Transcription, Genetic, Unfolded Protein Response, X-Box Binding Protein 1, N-glycosylation, proteostasis, glycoproteome, lectin microarray, endoplasmic reticulum, Hela Cells
Abstract

Classically, the unfolded protein response (UPR) safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated spliced X-box binding protein 1 (XBP1s)-mediated response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s activation for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional output of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. For example, XBP1s activity decreased levels of sialylation and bisecting GlcNAc in the HEK293 membrane proteome and secretome, while substantially increasing the population of oligomannose N-glycans only in the secretome. In HeLa cell membranes, stress-independent XBP1s activation increased the population of high-mannose and tetraantennary N-glycans, and also enhanced core fucosylation. mRNA profiling experiments suggest that XBP1s-mediated remodeling of the N-glycome is, at least in part, a consequence of coordinated transcriptional resculpting of N-glycan maturation pathways by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s can act as a master regulator of N-glycan maturation. Moreover, because the sugars on cell-surface proteins or on proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling into altered interactions with the extracellular environment.

Published
2018

11. Cell-specific bioorthogonal tagging of glycoproteins

Author

Cioce, Anna, Calle, Beatriz, Rizou, Tatiana, Lowery, Sarah C., Bridgeman, Victoria L., Mahoney, Keira E., Marchesi, Andrea, Bineva-Todd, Ganka, Flynn, Helen, Li, Zhen, Tastan, Omur Y., Roustan, Chloe, Soro-Barrio, Pablo, Rafiee, Mahmoud-Reza, Garza-Garcia, Acely, Antonopoulos, Aristotelis, Wood, Thomas M., Keenan, Tessa, Both, Peter, Huang, Kun, Parmeggian, Fabio, Snijders, Ambrosius P., Skehel, Mark, Kjær, Svend, Fascione, Martin A., Bertozzi, Carolyn R., Haslam, Stuart M., Flitsch, Sabine L., Malaker, Stacy A., Malanchi, Ilaria, and Schumann, Benjamin

Published
2022
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14. Metabolic precision labeling enables selective probing of O-linked N -acetylgalactosamine glycosylation

Author

Debets, Marjoke F., Tastan, Omur Y., Wisnovsky, Simon P., Malaker, Stacy A., Angelis, Nikolaos, Moeckl, Leonhard K. R., Choi, Junwon, Flynn, Helen, Wagner, Lauren J. S., Bineva-Todd, Ganka, Antonopoulos, Aristotelis, Cioce, Anna, Browne, William M., Li, Zhen, Briggs, David C., Douglas, Holly L., Hess, Gaelen T., Agbay, Anthony J., Roustan, Chloe, Kjaer, Svend, Haslam, Stuart M., Snijders, Ambrosius P., Bassik, Michael C., Moerner, W. E., Li, Vivian S. W., Bertozzi, Carolyn R., and Schumann, Benjamin

Published
2020

19. Decreased fucosylation impacts epithelial integrity and increases risk for COPD

Author

Swaby, Carter, primary, Yeung-Luk, Bonnie, additional, Thapa, Shreeti, additional, Nishida, Kristine, additional, Wally, Arabelis, additional, Ghosh, Baishakhi, additional, Niederkofler, Austin, additional, Luk, Sean, additional, Girgis, Mirit, additional, Keller, Allison, additional, Cortez, Cecilia, additional, Ramaswamy, Sahana, additional, Wilmsen, Kai, additional, Bouché, Laura, additional, Dell, Anne, additional, Drummond, M. Bradley, additional, Putcha, Nirupama, additional, Haslam, Stuart M., additional, Mathias, Rasika, additional, Hansel, Nadia N., additional, Sheng, Jian, additional, and Sidhaye, Venkataramana, additional

Published
2023
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22. Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance

Author

Cao, Huan, Antonopoulos, Aristotelis, Henderson, Sadie, Wassall, Heather, Brewin, John, Masson, Alanna, Shepherd, Jenna, Konieczny, Gabriela, Patel, Bhinal, Williams, Maria-Louise, Davie, Adam, Forrester, Megan A., Hall, Lindsay, Minter, Beverley, Tampakis, Dimitris, Moss, Michael, Lennon, Charlotte, Pickford, Wendy, Erwig, Lars, Robertson, Beverley, Dell, Anne, Brown, Gordon D., Wilson, Heather M., Rees, David C., Haslam, Stuart M., Alexandra Rowe, J., Barker, Robert N., and Vickers, Mark A.

Published
2021
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25. Hypomorphic homozygous mutations in phosphoglucomutase 3 (PGM3) impair immunity and increase serum IgE levels

Author

Sassi, Atfa, Lazaroski, Sandra, Wu, Gang, Haslam, Stuart M, Fliegauf, Manfred, Mellouli, Fethi, Patiroglu, Turkan, Unal, Ekrem, Ozdemir, Mehmet Akif, Jouhadi, Zineb, Khadir, Khadija, Ben-Khemis, Leila, Ben-Ali, Meriem, Ben-Mustapha, Imen, Borchani, Lamia, Pfeifer, Dietmar, Jakob, Thilo, Khemiri, Monia, Asplund, A Charlotta, Gustafsson, Manuela O, Lundin, Karin E, Falk-Sörqvist, Elin, Moens, Lotte N, Gungor, Hatice Eke, Engelhardt, Karin R, Dziadzio, Magdalena, Stauss, Hans, Fleckenstein, Bernhard, Meier, Rebecca, Prayitno, Khairunnadiya, Maul-Pavicic, Andrea, Schaffer, Sandra, Rakhmanov, Mirzokhid, Henneke, Philipp, Kraus, Helene, Eibel, Hermann, Kölsch, Uwe, Nadifi, Sellama, Nilsson, Mats, Bejaoui, Mohamed, Schäffer, Alejandro A, Smith, CI Edvard, Dell, Anne, Barbouche, Mohamed-Ridha, and Grimbacher, Bodo

Subjects
Biomedical and Clinical Sciences, Immunology, Clinical Research, Genetics, Rare Diseases, Emerging Infectious Diseases, Aetiology, 2.1 Biological and endogenous factors, Adult, Amino Acid Substitution, Cell Proliferation, Child, Chromosomes, Human, Pair 6, Female, Genetic Diseases, Inborn, Genetic Linkage, Glycosylation, Homozygote, Humans, Immunity, Immunoglobulin E, Infant, Job Syndrome, Male, Mutation, Missense, Phosphoglucomutase, T-Lymphocytes, Tunisia, Hyper-IgE syndrome, glycosylation, Staphylococcus aureus, signal transducer and activator of transcription 3, dedicator of cytokinesis 8, phosphoglucomutase 3, Allergy
Abstract

BackgroundRecurrent bacterial and fungal infections, eczema, and increased serum IgE levels characterize patients with the hyper-IgE syndrome (HIES). Known genetic causes for HIES are mutations in signal transducer and activator of transcription 3 (STAT3) and dedicator of cytokinesis 8 (DOCK8), which are involved in signal transduction pathways. However, glycosylation defects have not been described in patients with HIES. One crucial enzyme in the glycosylation pathway is phosphoglucomutase 3 (PGM3), which catalyzes a key step in the synthesis of uridine diphosphate N-acetylglucosamine, which is required for the biosynthesis of N-glycans.ObjectiveWe sought to elucidate the genetic cause in patients with HIES who do not carry mutations in STAT3 or DOCK8.MethodsAfter establishing a linkage interval by means of SNPchip genotyping and homozygosity mapping in 2 families with HIES from Tunisia, mutational analysis was performed with selector-based, high-throughput sequencing. Protein expression was analyzed by means of Western blotting, and glycosylation was profiled by using mass spectrometry.ResultsMutational analysis of candidate genes in an 11.9-Mb linkage region on chromosome 6 shared by 2 multiplex families identified 2 homozygous mutations in PGM3 that segregated with disease status and followed recessive inheritance. The mutations predict amino acid changes in PGM3 (p.Glu340del and p.Leu83Ser). A third homozygous mutation (p.Asp502Tyr) and the p.Leu83Ser variant were identified in 2 other affected families, respectively. These hypomorphic mutations have an effect on the biosynthetic reactions involving uridine diphosphate N-acetylglucosamine. Glycomic analysis revealed an aberrant glycosylation pattern in leukocytes demonstrated by a reduced level of tri-antennary and tetra-antennary N-glycans. T-cell proliferation and differentiation were impaired in patients. Most patients had developmental delay, and many had psychomotor retardation.ConclusionImpairment of PGM3 function leads to a novel primary (inborn) error of development and immunity because biallelic hypomorphic mutations are associated with impaired glycosylation and a hyper-IgE-like phenotype.

Published
2014

26. Profiling of glycan receptors for minute virus of mice in permissive cell lines towards understanding the mechanism of cell recognition.

Author

Halder, Sujata, Cotmore, Susan, Heimburg-Molinaro, Jamie, Smith, David F, Cummings, Richard D, Chen, Xi, Trollope, Alana J, North, Simon J, Haslam, Stuart M, Dell, Anne, Tattersall, Peter, McKenna, Robert, and Agbandje-McKenna, Mavis

Subjects
Lymphocytes, Cell Line, Fibroblasts, Animals, Humans, Mice, Virion, Capsid, N-Acetylneuraminic Acid, Microarray Analysis, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Minute virus of mice, Minute Virus of Mice, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, General Science & Technology
Abstract

The recognition of sialic acids by two strains of minute virus of mice (MVM), MVMp (prototype) and MVMi (immunosuppressive), is an essential requirement for successful infection. To understand the potential for recognition of different modifications of sialic acid by MVM, three types of capsids, virus-like particles, wild type empty (no DNA) capsids, and DNA packaged virions, were screened on a sialylated glycan microarray (SGM). Both viruses demonstrated a preference for binding to 9-O-methylated sialic acid derivatives, while MVMp showed additional binding to 9-O-acetylated and 9-O-lactoylated sialic acid derivatives, indicating recognition differences. The glycans recognized contained a type-2 Galβ1-4GlcNAc motif (Neu5Acα2-3Galβ1-4GlcNAc or 3'SIA-LN) and were biantennary complex-type N-glycans with the exception of one. To correlate the recognition of the 3'SIA-LN glycan motif as well as the biantennary structures to their natural expression in cell lines permissive for MVMp, MVMi, or both strains, the N- and O-glycans, and polar glycolipids present in three cell lines used for in vitro studies, A9 fibroblasts, EL4 T lymphocytes, and the SV40 transformed NB324K cells, were analyzed by MALDI-TOF/TOF mass spectrometry. The cells showed an abundance of the sialylated glycan motifs recognized by the viruses in the SGM and previous glycan microarrays supporting their role in cellular recognition by MVM. Significantly, the NB324K showed fucosylation at the non-reducing end of their biantennary glycans, suggesting that recognition of these cells is possibly mediated by the Lewis X motif as in 3'SIA-Le(X) identified in a previous glycan microarray screen.

Published
2014

27. Maternal-derived galectin-1 shapes the placenta niche through Sda terminal glycosylation: Implication for preeclampsia

Author

Xie, Yiran, primary, Zhao, Fangqi, additional, Freitag, Nancy, additional, Borowski, Sophia, additional, Wang, Yiru, additional, Harms, Charlotte, additional, Pang, Poh-Choo, additional, Desforges, Juliette, additional, Wen, Tianyu, additional, Schwedhelm, Edzard, additional, Singh, Manvendra, additional, Dechend, Ralf, additional, Dell, Anne, additional, Haslam, Stuart M, additional, Dveksler, Gabriela, additional, Garcia, Mariana G, additional, and Blois, Sandra M, additional

Published
2023
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28. Author Correction: Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis

Author

Kawahara, Rebeca, Chernykh, Anastasia, Alagesan, Kathirvel, Bern, Marshall, Cao, Weiqian, Chalkley, Robert J., Cheng, Kai, Choo, Matthew S., Edwards, Nathan, Goldman, Radoslav, Hoffmann, Marcus, Hu, Yingwei, Huang, Yifan, Kim, Jin Young, Kletter, Doron, Liquet, Benoit, Liu, Mingqi, Mechref, Yehia, Meng, Bo, Neelamegham, Sriram, Nguyen-Khuong, Terry, Nilsson, Jonas, Pap, Adam, Park, Gun Wook, Parker, Benjamin L., Pegg, Cassandra L., Penninger, Josef M., Phung, Toan K., Pioch, Markus, Rapp, Erdmann, Sakalli, Enes, Sanda, Miloslav, Schulz, Benjamin L., Scott, Nichollas E., Sofronov, Georgy, Stadlmann, Johannes, Vakhrushev, Sergey Y., Woo, Christina M., Wu, Hung-Yi, Yang, Pengyuan, Ying, Wantao, Zhang, Hui, Zhang, Yong, Zhao, Jingfu, Zaia, Joseph, Haslam, Stuart M., Palmisano, Giuseppe, Yoo, Jong Shin, Larson, Göran, Khoo, Kai-Hooi, Medzihradszky, Katalin F., Kolarich, Daniel, Packer, Nicolle H., and Thaysen-Andersen, Morten

Published
2022
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32. Endothelial galectin-1 binds to specific glycans on nipah virus fusion protein and inhibits maturation, mobility, and function to block syncytia formation.

Author

Garner, Omai B, Aguilar, Hector C, Fulcher, Jennifer A, Levroney, Ernest L, Harrison, Rebecca, Wright, Lacey, Robinson, Lindsey R, Aspericueta, Vanessa, Panico, Maria, Haslam, Stuart M, Morris, Howard R, Dell, Anne, Lee, Benhur, and Baum, Linda G

Subjects
Cells, Cultured, Endothelial Cells, Giant Cells, Humans, Nipah Virus, Henipavirus Infections, Polysaccharides, Galectin 1, Viral Fusion Proteins, Membrane Fusion, Protein Binding, Virus Physiological Phenomena, Cells, Cultured, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

Nipah virus targets human endothelial cells via NiV-F and NiV-G envelope glycoproteins, resulting in endothelial syncytia formation and vascular compromise. Endothelial cells respond to viral infection by releasing innate immune effectors, including galectins, which are secreted proteins that bind to specific glycan ligands on cell surface glycoproteins. We demonstrate that galectin-1 reduces NiV-F mediated fusion of endothelial cells, and that endogenous galectin-1 in endothelial cells is sufficient to inhibit syncytia formation. Galectin-1 regulates NiV-F mediated cell fusion at three distinct points, including retarding maturation of nascent NiV-F, reducing NiV-F lateral mobility on the plasma membrane, and directly inhibiting the conformational change in NiV-F required for triggering fusion. Characterization of the NiV-F N-glycome showed that the critical site for galectin-1 inhibition is rich in glycan structures known to bind galectin-1. These studies identify a unique set of mechanisms for regulating pathophysiology of NiV infection at the level of the target cell.

Published
2010

33. Supplementary Figure S4 from An In Vivo Functional Screen Identifies ST6GalNAc2 Sialyltransferase as a Breast Cancer Metastasis Suppressor

Author

Murugaesu, Nirupa, primary, Iravani, Marjan, primary, van Weverwijk, Antoinette, primary, Ivetic, Aleksandar, primary, Johnson, Damian A., primary, Antonopoulos, Aristotelis, primary, Fearns, Antony, primary, Jamal-Hanjani, Mariam, primary, Sims, David, primary, Fenwick, Kerry, primary, Mitsopoulos, Costas, primary, Gao, Qiong, primary, Orr, Nick, primary, Zvelebil, Marketa, primary, Haslam, Stuart M., primary, Dell, Anne, primary, Yarwood, Helen, primary, Lord, Christopher J., primary, Ashworth, Alan, primary, and Isacke, Clare M., primary

Published
2023
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34. Data from An In Vivo Functional Screen Identifies ST6GalNAc2 Sialyltransferase as a Breast Cancer Metastasis Suppressor

Author

Murugaesu, Nirupa, primary, Iravani, Marjan, primary, van Weverwijk, Antoinette, primary, Ivetic, Aleksandar, primary, Johnson, Damian A., primary, Antonopoulos, Aristotelis, primary, Fearns, Antony, primary, Jamal-Hanjani, Mariam, primary, Sims, David, primary, Fenwick, Kerry, primary, Mitsopoulos, Costas, primary, Gao, Qiong, primary, Orr, Nick, primary, Zvelebil, Marketa, primary, Haslam, Stuart M., primary, Dell, Anne, primary, Yarwood, Helen, primary, Lord, Christopher J., primary, Ashworth, Alan, primary, and Isacke, Clare M., primary

Published
2023
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35. Supplementary Movie S2 from An In Vivo Functional Screen Identifies ST6GalNAc2 Sialyltransferase as a Breast Cancer Metastasis Suppressor

Author

Murugaesu, Nirupa, primary, Iravani, Marjan, primary, van Weverwijk, Antoinette, primary, Ivetic, Aleksandar, primary, Johnson, Damian A., primary, Antonopoulos, Aristotelis, primary, Fearns, Antony, primary, Jamal-Hanjani, Mariam, primary, Sims, David, primary, Fenwick, Kerry, primary, Mitsopoulos, Costas, primary, Gao, Qiong, primary, Orr, Nick, primary, Zvelebil, Marketa, primary, Haslam, Stuart M., primary, Dell, Anne, primary, Yarwood, Helen, primary, Lord, Christopher J., primary, Ashworth, Alan, primary, and Isacke, Clare M., primary

Published
2023
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36. Supplementary Material from An In Vivo Functional Screen Identifies ST6GalNAc2 Sialyltransferase as a Breast Cancer Metastasis Suppressor

Author

Murugaesu, Nirupa, primary, Iravani, Marjan, primary, van Weverwijk, Antoinette, primary, Ivetic, Aleksandar, primary, Johnson, Damian A., primary, Antonopoulos, Aristotelis, primary, Fearns, Antony, primary, Jamal-Hanjani, Mariam, primary, Sims, David, primary, Fenwick, Kerry, primary, Mitsopoulos, Costas, primary, Gao, Qiong, primary, Orr, Nick, primary, Zvelebil, Marketa, primary, Haslam, Stuart M., primary, Dell, Anne, primary, Yarwood, Helen, primary, Lord, Christopher J., primary, Ashworth, Alan, primary, and Isacke, Clare M., primary

Published
2023
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38. Altered glycosylation of glycodelin in endometrial carcinoma

Author

Hautala, Laura C., Pang, Poh-Choo, Antonopoulos, Aristotelis, Pasanen, Annukka, Lee, Cheuk-Lun, Chiu, Philip C. N., Yeung, William S. B., Loukovaara, Mikko, Bützow, Ralf, Haslam, Stuart M., Dell, Anne, and Koistinen, Hannu

Abstract

Glycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Galβ1–4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins.

Published
2024
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48. Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology.

Author

Zhengyuan Huang, Lai, Pei F., Cocker, Alexander T. H., Haslam, Stuart M., Dell, Anne, Brady, Hugh J. M., and Johnson, Mark R.

Subjects
TROPHOBLAST, POST-translational modification, NEOVASCULARIZATION, PATHOLOGICAL physiology, MOLAR pregnancy, PREGNANCY complications, GLYCOSYLATION
Abstract

Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by Nglycan-BP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of Nglycosylated proteins, and how these cells receive decidua-derived signals via N-glycan-GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more indepth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction. [ABSTRACT FROM AUTHOR]

Published
2023
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