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Glycosylation and Glycoproteins
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Glycosylation and Glycoproteins

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 October 2015) | Viewed by 185010

Special Issue Editors

Prof. Dr. Patricia Berninsone

E-Mail Website
Guest Editor
Department of Biology, University of Nevada Reno, Reno, NV, USA
Interests: protein glycosylation; regulation of glycosylation reactions; roles of glycosylation in development and disease
Special Issues, Collections and Topics in MDPI journals
Assoc. Prof. Dr. Joe Tiralongo

E-Mail Website
Co-Guest Editor
Institute for Glycomics, Gold Coast Campus, Griffith University, Queensland 4222, Australia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Sugars, which represent one of the four fundamental building blocks of life, are the most abundant biological molecules on our planet. Sugars can be combined in a myriad number of ways to form complex carbohydrate structures (glycans). The glycan repertoire (glycome) of a given cell or organism is thus many orders of magnitude more complex than the genome or the proteome. However, only over the past two decades have we begun to truly appreciate the extent to which glycan function permeates biological systems, including human health and disease.
Glycosylation is the process by which a sugar is enzymatically attached to proteins, lipids, or other organic molecules. In particular, glycosylation increases protein diversity and structure, and as such significantly impacts on the function of the resulting glycoprotein.
As the roles of glycosylation in physiological and pathological processes are increasingly being recognized, the field of glycobiology is eliciting an unprecedented interest. However, the extreme complexity and structural diversity of glycans, combined with their “non-template”-driven synthesis, pose a significant technical challenge that has stimulated advances in the field.
This Special Issue will welcome contributions in all areas of glycobiology, including studies on the function of glycans in basic biological processes and human diseases, and the regulation of glycosylation reactions in vivo, as well as technical advances to analyze the complexities of the glycoproteome.

Prof. Dr. Patricia Berninsone
Dr. Joe Tiralongo
Guest Editors

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed Open Access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF.

Keywords

  • glycosylation
  • carbohydrate
  • glycosyl donor
  • glycosyl acceptor
  • glycan
  • protein
  • lipid
  • co-translation
  • post-translation
  • glypiation
  • glycosidic bond
  • mannosylation
  • oligosaccharide chain
  • glycoprotein
  • protein
  • mucins
  • glycoprotein IIb/IIIa
  • zona pellucida
  • miraculin
  • transferrin
  • ceruloplasmin
  • immunoglobins
  • histocompatibility antigens
  • human chorionic gonadotropin (HCG)
  • thyroid-stimulating hormone (TSH)
  • patatin
  • lectin
  • selectin
  • calnexin
  • calreticulin

Published Papers (22 papers)

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4881 KiB  
Article
N-Glycosylation of Human R-Spondin 1 Is Required for Efficient Secretion and Stability but Not for Its Heparin Binding Ability
by Chiung-Fang Chang, Li-Sung Hsu, Chieh-Yu Weng, Chih-Kai Chen, Shu-Ying Wang, Yi-Hwa Chou, Yan-Yu Liu, Zi-Xiu Yuan, Wen-Ying Huang, Ho Lin, Yau-Hung Chen and Jen-Ning Tsai
Int. J. Mol. Sci. 2016, 17(6), 937; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17060937 - 14 Jun 2016
Cited by 8 | Viewed by 9604
Abstract
R-spondin 1 (Rspo1) plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, [...] Read more.
R-spondin 1 (Rspo1) plays an essential role in stem cell biology by potentiating Wnt signaling activity. Despite the fact that Rspo1 holds therapeutic potential for a number of diseases, its biogenesis is not fully elucidated. All Rspo proteins feature two amino-terminal furin-like repeats, which are responsible for Wnt signal potentiation, and a thrombospondin type 1 (TSR1) domain that can provide affinity towards heparan sulfate proteoglycans. Using chemical inhibitors, deglycosylase and site-directed mutagenesis, we found that human Rspo1 and Rspo3 are both N-glycosylated at N137, a site near the C-terminus of the furin repeat 2 domain, and Rspo2 is N-glycosylated at N160, a position near the N-terminus of TSR1 domain. Elimination of N-glycosylation at these sites affects their accumulation in media but have no effect on the ability towards heparin. Introduction of the N-glycosylation site to Rspo2 mutant at the position homologous to N137 in Rspo1 restored full glycosylation and rescued the accumulation defect of nonglycosylated Rspo2 mutant in media. Similar effect can be observed in the N137 Rspo1 or Rspo3 mutant engineered with Rspo2 N-glycosylation site. The results highlight the importance of N-glycosylation at these two positions in efficient folding and secretion of Rspo family. Finally, we further showed that human Rspo1 is subjected to endoplasmic reticulum (ER) quality control in N-glycan-dependent manner. While N-glycan of Rspo1 plays a role in its intracellular stability, it had little effect on secreted Rspo1. Our findings provide evidence for the critical role of N-glycosylation in the biogenesis of Rspo1. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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4177 KiB  
Article
Ultra-Fast Glyco-Coating of Non-Biological Surfaces
by Eleanor Williams, Katie Barr, Elena Korchagina, Alexander Tuzikov, Stephen Henry and Nicolai Bovin
Int. J. Mol. Sci. 2016, 17(1), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17010118 - 16 Jan 2016
Cited by 13 | Viewed by 6237
Abstract
The ability to glycosylate surfaces has medical and diagnostic applications, but there is no technology currently recognized as being able to coat any surface without the need for prior chemical modification of the surface. Recently, a family of constructs called function-spacer-lipids (FSL) has [...] Read more.
The ability to glycosylate surfaces has medical and diagnostic applications, but there is no technology currently recognized as being able to coat any surface without the need for prior chemical modification of the surface. Recently, a family of constructs called function-spacer-lipids (FSL) has been used to glycosylate cells. Because it is known that lipid-based material can adsorb onto surfaces, we explored the potential and performance of cell-labelling FSL constructs to “glycosylate” non-biological surfaces. Using blood group A antigen as an indicator, the performance of a several variations of FSL constructs to modify a large variety of non-biological surfaces was evaluated. It was found the FSL constructs when optimised could in a few seconds glycosylate almost any non-biological surface including metals, glass, plastics, rubbers and other polymers. Although the FSL glycan coating was non-covalent, and therefore temporary, it was sufficiently robust with appropriate selection of spacer and surface that it could capture anti-glycan antibodies, immobilize cells (via antibody), and withstand incubation in serum and extensive buffer washing, making it suitable for diagnostic and research applications. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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1547 KiB  
Article
Post-Translational Modification and Secretion of Azelaic Acid Induced 1 (AZI1), a Hybrid Proline-Rich Protein from Arabidopsis
by Andrea Pitzschke, Hui Xue, Helene Persak, Sneha Datta and Georg J. Seifert
Int. J. Mol. Sci. 2016, 17(1), 85; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17010085 - 12 Jan 2016
Cited by 10 | Viewed by 6598
Abstract
Arabidopsis EARLI-type hybrid proline-rich proteins (HyPRPs) consist of a putative N-terminal secretion signal, a proline-rich domain (PRD), and a characteristic eight-cysteine-motif (8-CM). They have been implicated in biotic and abiotic stress responses. AZI1 is required for systemic acquired resistance and it has recently [...] Read more.
Arabidopsis EARLI-type hybrid proline-rich proteins (HyPRPs) consist of a putative N-terminal secretion signal, a proline-rich domain (PRD), and a characteristic eight-cysteine-motif (8-CM). They have been implicated in biotic and abiotic stress responses. AZI1 is required for systemic acquired resistance and it has recently been identified as a target of the stress-induced mitogen-activated protein kinase MPK3. AZI1 gel migration properties strongly indicate AZI1 to undergo major post-translational modifications. These occur in a stress-independent manner and are unrelated to phosphorylation by MAPKs. As revealed by transient expression of AZI1 in Nicotiana benthamiana and Tropaeolum majus, the Arabidopsis protein is similarly modified in heterologous plant species. Proline-rich regions, resembling arabinogalactan proteins point to a possible proline hydroxylation and subsequent O-glycosylation of AZI1. Consistently, inhibition of prolyl hydroxylase reduces its apparent protein size. AZI1 secretion was examined using Arabidopsis protoplasts and seedling exudates. Employing Agrobacterium-mediated leaf infiltration of N. benthamiana, we attempted to assess long-distance movement of AZI1. In summary, the data point to AZI1 being a partially secreted protein and a likely new member of the group of hydroxyproline-rich glycoproteins. Its dual location suggests AZI1 to exert both intra- and extracellular functions. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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2365 KiB  
Article
Polar Glycosylated and Lateral Non-Glycosylated Flagella from Aeromonas hydrophila Strain AH-1 (Serotype O11)
by Kelly M. Fulton, Elena Mendoza-Barberá, Susan M. Twine, Juan M. Tomás and Susana Merino
Int. J. Mol. Sci. 2015, 16(12), 28255-28269; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161226097 - 27 Nov 2015
Cited by 11 | Viewed by 5796
Abstract
Polar and but not lateral flagellin proteins from Aeromonas hydrophila strain AH-1 (serotype O11) were found to be glycosylated. Top-down mass spectrometry studies of purified polar flagellins suggested the presence of a 403 Da glycan of mass. Bottom-up mass spectrometry studies showed the [...] Read more.
Polar and but not lateral flagellin proteins from Aeromonas hydrophila strain AH-1 (serotype O11) were found to be glycosylated. Top-down mass spectrometry studies of purified polar flagellins suggested the presence of a 403 Da glycan of mass. Bottom-up mass spectrometry studies showed the polar flagellin peptides to be modified with 403 Da glycans in O-linkage. The MS fragmentation pattern of this putative glycan was similar to that of pseudaminic acid derivative. Mutants lacking the biosynthesis of pseudaminic acid (pseB and pseI homologues) were unable to produce polar flagella but no changes were observed in lateral flagella by post-transcriptional regulation of the flagellin. Complementation was achieved by reintroduction of the wild-type pseB and pseI. We compared two pathogenic features (adhesion to eukaryotic cells and biofilm production) between the wild-type strain and two kinds of mutants: mutants lacking polar flagella glycosylation and lacking the O11-antigen lipopolysaccharide (LPS) but with unaltered polar flagella glycosylation. Results suggest that polar flagella glycosylation is extremely important for A. hydrophila AH-1 adhesion to Hep-2 cells and biofilm formation. In addition, we show the importance of the polar flagella glycosylation for immune stimulation of IL-8 production via toll-“like” receptor 5 (TLR5). Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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4330 KiB  
Article
The Role of PTP1B O-GlcNAcylation in Hepatic Insulin Resistance
by Yun Zhao, Zhuqi Tang, Aiguo Shen, Tao Tao, Chunhua Wan, Xiaohui Zhu, Jieru Huang, Wanlu Zhang, Nana Xia, Suxin Wang, Shiwei Cui and Dongmei Zhang
Int. J. Mol. Sci. 2015, 16(9), 22856-22869; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160922856 - 22 Sep 2015
Cited by 24 | Viewed by 6299
Abstract
Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several [...] Read more.
Protein tyrosine phosphatase 1B (PTP1B), which can directly dephosphorylate both the insulin receptor and insulin receptor substrate 1 (IRS-1), thereby terminating insulin signaling, reportedly plays an important role in insulin resistance. Accumulating evidence has demonstrated that O-GlcNAc modification regulates functions of several important components of insulin signal pathway. In this study, we identified that PTP1B is modified by O-GlcNAcylation at three O-GlcNAc sites (Ser104, Ser201, and Ser386). Palmitate acid (PA) impaired the insulin signaling, indicated by decreased phosphorylation of both serine/threonine-protein kinase B (Akt) and glycogen synthase kinase 3 beta (GSK3β) following insulin administration, and upregulated PTP1B O-GlcNAcylation in HepG2 cells. Compared with the wild-type, intervention PTP1B O-GlcNAcylation by site-directed gene mutation inhibited PTP1B phosphatase activity, resulted in a higher level of phosphorylated Akt and GSK3β, recovered insulin sensitivity, and improved lipid deposition in HepG2 cells. Taken together, our research showed that O-GlcNAcylation of PTP1B can influence insulin signal transduction by modulating its own phosphatase activity, which participates in the process of hepatic insulin resistance. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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2034 KiB  
Article
NOS1AP O-GlcNAc Modification Involved in Neuron Apoptosis Induced by Excitotoxicity
by Liang Zhu, Tao Tao, Dongmei Zhang, Xiaojuan Liu, Kaifu Ke and Aiguo Shen
Int. J. Mol. Sci. 2015, 16(7), 16560-16575; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160716560 - 21 Jul 2015
Cited by 11 | Viewed by 6222
Abstract
O-Linked N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational modification that cycles on and off serine and threonine residues of nucleocytoplasmic and mitochondrial proteins. In addition to cancer and inflammation diseases, O-GlcNAc modification appears to play a critical role during [...] Read more.
O-Linked N-acetylglucosamine, or O-GlcNAc, is a dynamic post-translational modification that cycles on and off serine and threonine residues of nucleocytoplasmic and mitochondrial proteins. In addition to cancer and inflammation diseases, O-GlcNAc modification appears to play a critical role during cell apoptosis and stress response, although the precise mechanisms are still not very clear. Here we found that nitric oxide synthase adaptor (NOS1AP), which plays an important part in glutamate-induced neuronal apoptosis, carries the modification of O-GlcNAc. Mass spectrometry analysis identified Ser47, Ser183, Ser204, Ser269, Ser271 as O-GlcNAc sites. Higher O-GlcNAc of NOS1AP was detected during glutamate-induced neuronal apoptosis. Furthermore, with O-GlcNAc sites of NOS1AP mutated, the interaction of NOS1AP and neuronal nitric oxide syntheses (nNOS) decreases. Finally, during glutamate-induced neuronal apoptosis, decreasing the O-GlcNAc modification of NOS1AP results in more severe neuronal apoptosis. All these results suggest that O-GlcNAc modification of NOS1AP exerts protective effects during glutamate-induced neuronal apoptosis. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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2882 KiB  
Article
Terminal Mannose Residues in Seminal Plasma Glycoproteins of Infertile Men Compared to Fertile Donors
by Beata Olejnik, Anna Jarząb, Ewa M. Kratz, Mariusz Zimmer, Andrzej Gamian and Mirosława Ferens-Sieczkowska
Int. J. Mol. Sci. 2015, 16(7), 14933-14950; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160714933 - 02 Jul 2015
Cited by 12 | Viewed by 6323
Abstract
The impact of seminal plasma components on the fertilization outcomes in humans is still under question. The increasing number of couples facing problems with conception raises the need for predictive biomarkers. Detailed understanding of the molecular mechanisms accompanying fertilization remains another challenge. Carbohydrate–protein [...] Read more.
The impact of seminal plasma components on the fertilization outcomes in humans is still under question. The increasing number of couples facing problems with conception raises the need for predictive biomarkers. Detailed understanding of the molecular mechanisms accompanying fertilization remains another challenge. Carbohydrate–protein recognition may be of key importance in this complex field. In this study, we analyzed the unique glycosylation pattern of seminal plasma proteins, the display of high-mannose and hybrid-type oligosaccharides, by means of their reactivity with mannose-specific Galanthus nivalis lectin. Normozoospermic infertile subjects presented decreased amounts of lectin-reactive glycoepitopes compared to fertile donors and infertile patients with abnormal semen parameters. Glycoproteins containing unveiled mannose were isolated in affinity chromatography, and 17 glycoproteins were identified in liquid chromatography-tandem mass spectrometry with electrospray ionization. The N-glycome of the isolated glycoproteins was examined in matrix-assisted laser desorption ionization mass spectrometry. Eleven out of 27 identified oligosaccharides expressed terminal mannose residues, responsible for lectin binding. We suggest that lowered content of high-mannose and hybrid type glycans in normozoospermic infertile patients may be associated with impaired sperm protection from preterm capacitation and should be considered in the search for new infertility markers. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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1403 KiB  
Article
Enzymatic Synthesis of Galactosylated Serine/Threonine Derivatives by β-Galactosidase from Escherichia coli
by Sooyoun Seo, Joseph Rebehmed, Alexandre G. De Brevern and Salwa Karboune
Int. J. Mol. Sci. 2015, 16(6), 13714-13728; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms160613714 - 15 Jun 2015
Cited by 4 | Viewed by 7334
Abstract
The transgalactosylations of serine/threonine derivatives were investigated using β-galactosidase from Escherichia coli as biocatalyst. Using ortho-nitrophenyl-β-D-galactoside as donor, the highest bioconversion yield of transgalactosylated N-carboxy benzyl L-serine benzyl ester (23.2%) was achieved in heptane:buffer medium (70:30), whereas with the lactose, the [...] Read more.
The transgalactosylations of serine/threonine derivatives were investigated using β-galactosidase from Escherichia coli as biocatalyst. Using ortho-nitrophenyl-β-D-galactoside as donor, the highest bioconversion yield of transgalactosylated N-carboxy benzyl L-serine benzyl ester (23.2%) was achieved in heptane:buffer medium (70:30), whereas with the lactose, the highest bioconversion yield (3.94%) was obtained in the buffer reaction system. The structures of most abundant galactosylated serine products were characterized by MS/MS. The molecular docking simulation revealed that the binding of serine/threonine derivatives to the enzyme’s active site was stronger (−4.6~−7.9 kcal/mol) than that of the natural acceptor, glucose, and mainly occurred through interactions with aromatic residues. For N-tert-butoxycarbonyl serine methyl ester (6.8%) and N-carboxybenzyl serine benzyl ester (3.4%), their binding affinities and the distances between their hydroxyl side chain and the 1′-OH group of galactose moiety were in good accordance with the quantified bioconversion yields. Despite its lower predicted bioconversion yield, the high experimental bioconversion yield obtained with N-carboxybenzyl serine methyl ester (23.2%) demonstrated the importance of the thermodynamically-driven nature of the transgalactosylation reaction. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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932 KiB  
Article
Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation
by Philip M. Jedrzejewski, Ioscani Jimenez Del Val, Antony Constantinou, Anne Dell, Stuart M. Haslam, Karen M. Polizzi and Cleo Kontoravdi
Int. J. Mol. Sci. 2014, 15(3), 4492-4522; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15034492 - 14 Mar 2014
Cited by 69 | Viewed by 11130
Abstract
Glycoproteins represent the largest group of the growing number of biologically-derived medicines. The associated glycan structures and their distribution are known to have a large impact on pharmacokinetics. A modelling framework was developed to provide a link from the extracellular environment and its [...] Read more.
Glycoproteins represent the largest group of the growing number of biologically-derived medicines. The associated glycan structures and their distribution are known to have a large impact on pharmacokinetics. A modelling framework was developed to provide a link from the extracellular environment and its effect on intracellular metabolites to the distribution of glycans on the constant region of an antibody product. The main focus of this work is the mechanistic in silico reconstruction of the nucleotide sugar donor (NSD) metabolic network by means of 34 species mass balances and the saturation kinetics rates of the 60 metabolic reactions involved. NSDs are the co-substrates of the glycosylation process in the Golgi apparatus and their simulated dynamic intracellular concentration profiles were linked to an existing model describing the distribution of N-linked glycan structures of the antibody constant region. The modelling framework also describes the growth dynamics of the cell population by means of modified Monod kinetics. Simulation results match well to experimental data from a murine hybridoma cell line. The result is a modelling platform which is able to describe the product glycoform based on extracellular conditions. It represents a first step towards the in silico prediction of the glycoform of a biotherapeutic and provides a platform for the optimisation of bioprocess conditions with respect to product quality. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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851 KiB  
Article
Genes Involved in the Endoplasmic Reticulum N-Glycosylation Pathway of the Red Microalga Porphyridium sp.: A Bioinformatic Study
by Oshrat Levy-Ontman, Merav Fisher, Yoram Shotland, Yacob Weinstein, Yoram Tekoah and Shoshana Malis Arad
Int. J. Mol. Sci. 2014, 15(2), 2305-2326; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15022305 - 07 Feb 2014
Cited by 24 | Viewed by 9098
Abstract
N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is [...] Read more.
N-glycosylation is one of the most important post-translational modifications that influence protein polymorphism, including protein structures and their functions. Although this important biological process has been extensively studied in mammals, only limited knowledge exists regarding glycosylation in algae. The current research is focused on the red microalga Porphyridium sp., which is a potentially valuable source for various applications, such as skin therapy, food, and pharmaceuticals. The enzymes involved in the biosynthesis and processing of N-glycans remain undefined in this species, and the mechanism(s) of their genetic regulation is completely unknown. In this study, we describe our pioneering attempt to understand the endoplasmic reticulum N-Glycosylation pathway in Porphyridium sp., using a bioinformatic approach. Homology searches, based on sequence similarities with genes encoding proteins involved in the ER N-glycosylation pathway (including their conserved parts) were conducted using the TBLASTN function on the algae DNA scaffold contigs database. This approach led to the identification of 24 encoded-genes implicated with the ER N-glycosylation pathway in Porphyridium sp. Homologs were found for almost all known N-glycosylation protein sequences in the ER pathway of Porphyridium sp.; thus, suggesting that the ER-pathway is conserved; as it is in other organisms (animals, plants, yeasts, etc.). Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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1241 KiB  
Article
Advanced Glycation End Product-Induced Astrocytic Differentiation of Cultured Neurospheres through Inhibition of Notch-Hes1 Pathway-Mediated Neurogenesis
by Yijing Guo, Pin Wang, Haixia Sun, Rongrong Cai, Wenqing Xia and Shaohua Wang
Int. J. Mol. Sci. 2014, 15(1), 159-170; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15010159 - 23 Dec 2013
Cited by 13 | Viewed by 8208
Abstract
This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell [...] Read more.
This study aims to investigate the roles of the Notch-Hes1 pathway in the advanced glycation end product (AGE)-mediated differentiation of neural stem cells (NSCs). We prepared pLentiLox3.7 lentiviral vectors that express short hairpin RNA (shRNA) against Notch1 and transfected it into NSCs. Cell differentiation was analyzed under confocal laser-scanning microscopy. The percentage of neurons and astrocytes was quantified by normalizing the total number of TUJ1+ (Neuron-specific class III β-tubulin) and GFAP+ (Glial fibrillary acidic protein) cells to the total number of Hoechst 33342-labeled cell nuclei. The protein and gene expression of Notch-Hes1 pathway components was examined via western blot analysis and real-time PCR. After 1 week of incubation, we found that AGE-bovine serum albumin (BSA) (400 μg/mL) induced the astrocytic differentiation of cultured neurospheres and inhibited neuronal formation. The expression of Notch-Hes1 pathway components was upregulated in the cells in the AGE-BSA culture medium. Immunoblot analysis indicated that shRNA silencing of Notch1 expression in NSCs significantly increases neurogenesis and suppresses astrocytic differentiation in NSCs incubated with AGE-BSA. AGEs promote the astrocytic differentiation of cultured neurospheres by inhibiting neurogenesis through the Notch-Hes1 pathway, providing a potential therapeutic target for hyperglycemia-related cognitive deficits. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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1384 KiB  
Article
Different Effects of Androgen on the Expression of Fut1, Fut2, Fut4 and Fut9 in Male Mouse Reproductive Tract
by Chun-Mei Wang, Shuang-Gang Hu, Yan-Fei Ru, Guang-Xin Yao, Wu-Bin Ma, Yi-Hua Gu, Chen Chu, Shou-Lin Wang, Zuo-Min Zhou, Qiang Liu, Yu-Chuan Zhou and Yong-Lian Zhang
Int. J. Mol. Sci. 2013, 14(11), 23188-23202; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141123188 - 21 Nov 2013
Cited by 5 | Viewed by 7153
Abstract
The α-(1,2) fucosyltransferases (Fut1 and Fut2) and α-(1,3) fucosyltransferases (Fut4, Fut9) are responsible for the synthesis of Lewis X (LeX) and Lewis Y (LeY) conjugated to glycoproteins. We recently reported that these fucosyltransferases were differentially expressed in the [...] Read more.
The α-(1,2) fucosyltransferases (Fut1 and Fut2) and α-(1,3) fucosyltransferases (Fut4, Fut9) are responsible for the synthesis of Lewis X (LeX) and Lewis Y (LeY) conjugated to glycoproteins. We recently reported that these fucosyltransferases were differentially expressed in the reproductive tract of male mouse. Here, we studied the effect of androgen on fucosyltransferase expression through the use of mouse castration models. We found that Fut1 mRNA and Fut4 mRNA were upregulated, while Fut2 mRNA and Fut9 mRNA were downregulated by androgen in the caput epididymis. However, in the vas deferens and prostate, only Fut4 mRNA and Fut2 mRNA were respectively upregulated following exposure to androgen. In the seminal vesicle, all fucosyltransferases, with the exception of Fut9, were upregulated. We identified the androgen receptor binding sites (ARBSs) of Fut2, Fut4 and Fut9 in the caput epididymis. Luciferase assay for these ARBSs is able to provide an indication as to why Fut4 and Fut9 are differently expressed and regulated by androgen, although they catalyze the same α-(1,3) fucose linkage. Our study showed that androgen could differentially regulate the expression of these fucosyltransferases and provided an insight into the characteristic distribution of each fucosyltransferase responsible for LeX/LeY biosynthesis in the male reproductive tract. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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490 KiB  
Article
The Key Enzyme of the Sialic Acid Metabolism Is Involved in Embryoid Body Formation and Expression of Marker Genes of Germ Layer Formation
by Wenke Weidemann, Jessica Hering, Dorit Bennmann, Annett Thate and Rüdiger Horstkorte
Int. J. Mol. Sci. 2013, 14(10), 20555-20563; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020555 - 14 Oct 2013
Cited by 6 | Viewed by 6462
Abstract
The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are [...] Read more.
The bi-functional enzyme UDP-N-acetyl-2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme of the sialic acid biosynthesis. Sialic acids are negatively charged nine carbon amino sugars and are found on most glycoproteins and many glycolipids in terminal positions, where they are involved in a variety of biological important molecular interactions. Inactivation of the GNE by homologous recombination results in early embryonic lethality in mice. Here, we report that GNE-deficient embryonic stem cells express less differentiation markers compared to wild-type embryonic stem cells. As a result, GNE-deficient embryonic stem cells fail to form proper embryoid bodies (EB) within the first day of culture. However, when culturing these cells in the presence of sialic acids for three days, also GNE-deficient embryonic stem cells form normal EBs. In contrast, when culturing these cells in sialic acid reduced medium, GNE-deficient embryonic stem cells proliferate faster and form larger EBs without any change in the expression of markers of the germ layers. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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333 KiB  
Article
Decreased Expression of Alpha-L-Fucosidase Gene FUCA1 in Human Colorectal Tumors
by Olalla Otero-Estévez, Mónica Martínez-Fernández, Lorena Vázquez-Iglesias, María Páez de la Cadena, Francisco J. Rodríguez-Berrocal and Vicenta S. Martínez-Zorzano
Int. J. Mol. Sci. 2013, 14(8), 16986-16998; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms140816986 - 19 Aug 2013
Cited by 23 | Viewed by 8142
Abstract
In previous studies we described a decreased alpha-L-fucosidase activity in colorectal tumors, appearing as a prognostic factor of tumoral recurrence. The aim of this work was to extend the knowledge about tissue alpha-L-fucosidase in colorectal cancer by quantifying the expression of its encoding [...] Read more.
In previous studies we described a decreased alpha-L-fucosidase activity in colorectal tumors, appearing as a prognostic factor of tumoral recurrence. The aim of this work was to extend the knowledge about tissue alpha-L-fucosidase in colorectal cancer by quantifying the expression of its encoding gene FUCA1 in tumors and healthy mucosa. FUCA1 mRNA levels were measured by RT-qPCR in paired tumor and normal mucosa tissues from 31 patients. For the accuracy of the RT-qPCR results, five candidate reference genes were validated in those samples. In addition, activity and expression of alpha-L-fucosidase in selected matched tumor and healthy mucosa samples were analyzed. According to geNorm and NormFinder algorithms, RPLP0 and HPRT1 were the best reference genes in colorectal tissues. These genes were used for normalization of FUCA1 expression levels. A significant decrease of more than 60% in normalized FUCA1 expression was detected in tumors compared to normal mucosa (p = 0.002). Moreover, a gradual decrease in FUCA1 expression was observed with progression of disease from earlier to advanced stages. These findings were confirmed by Western blot analysis of alpha-L-fucosidase expression. Our results demonstrated diminished FUCA1 mRNA levels in tumors, suggesting that expression of tissue alpha-L-fucosidase could be regulated at transcriptional level in colorectal cancer. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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Review

Jump to: Research

822 KiB  
Review
The Autonomous Glycosylation of Large DNA Viruses
by Francesco Piacente, Matteo Gaglianone, Maria Elena Laugieri and Michela G. Tonetti
Int. J. Mol. Sci. 2015, 16(12), 29315-29328; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161226169 - 09 Dec 2015
Cited by 27 | Viewed by 6181
Abstract
Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their nascent glycoproteins. In recent years, a newly discovered group of eukaryotic viruses, belonging to the Nucleo-Cytoplasmic Large DNA Virus [...] Read more.
Glycosylation of surface molecules is a key feature of several eukaryotic viruses, which use the host endoplasmic reticulum/Golgi apparatus to add carbohydrates to their nascent glycoproteins. In recent years, a newly discovered group of eukaryotic viruses, belonging to the Nucleo-Cytoplasmic Large DNA Virus (NCLDV) group, was shown to have several features that are typical of cellular organisms, including the presence of components of the glycosylation machinery. Starting from initial observations with the chlorovirus PBCV-1, enzymes for glycan biosynthesis have been later identified in other viruses; in particular in members of the Mimiviridae family. They include both the glycosyltransferases and other carbohydrate-modifying enzymes and the pathways for the biosynthesis of the rare monosaccharides that are found in the viral glycan structures. These findings, together with genome analysis of the newly-identified giant DNA viruses, indicate that the presence of glycogenes is widespread in several NCLDV families. The identification of autonomous viral glycosylation machinery leads to many questions about the origin of these pathways, the mechanisms of glycan production, and eventually their function in the viral replication cycle. The scope of this review is to highlight some of the recent results that have been obtained on the glycosylation systems of the large DNA viruses, with a special focus on the enzymes involved in nucleotide-sugar production. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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7108 KiB  
Review
Mass Spectrometry-Based N-Glycomics of Colorectal Cancer
by Manveen K. Sethi and Susan Fanayan
Int. J. Mol. Sci. 2015, 16(12), 29278-29304; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161226165 - 09 Dec 2015
Cited by 21 | Viewed by 10658
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases [...] Read more.
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide. An increased molecular understanding of the CRC pathology is warranted to gain insights into the underlying molecular and cellular mechanisms of the disease. Altered protein glycosylation patterns are associated with most diseases including malignant transformation. Recent advances in mass spectrometry and bioinformatics have accelerated glycomics research and present a new paradigm for cancer biomarker discovery. Mass spectrometry (MS)-based glycoproteomics and glycomics, therefore, hold considerable promise to improve the discovery of novel biomarkers with utility in disease diagnosis and therapy. This review focuses on the emerging field of glycomics to present a comprehensive review of advances in technologies and their application in studies aimed at discovering novel glycan-based biomarkers. We will also discuss some of the challenges associated with using glycans as biomarkers. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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2338 KiB  
Review
Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease
by Mohamed Ali Abol Hassan, Razina Rouf, Evelin Tiralongo, Tom W. May and Joe Tiralongo
Int. J. Mol. Sci. 2015, 16(4), 7802-7838; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms16047802 - 08 Apr 2015
Cited by 111 | Viewed by 10576
Abstract
Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein [...] Read more.
Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
656 KiB  
Review
Importance of N-Glycosylation on CD147 for Its Biological Functions
by Yang Bai, Wan Huang, Li-Tian Ma, Jian-Li Jiang and Zhi-Nan Chen
Int. J. Mol. Sci. 2014, 15(4), 6356-6377; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15046356 - 15 Apr 2014
Cited by 84 | Viewed by 10637
Abstract
Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various [...] Read more.
Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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194 KiB  
Review
P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases
by Andrea Picchianti-Diamanti, Maria Manuela Rosado, Marco Scarsella, Bruno Laganà and Raffaele D'Amelio
Int. J. Mol. Sci. 2014, 15(3), 4965-4976; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15034965 - 20 Mar 2014
Cited by 40 | Viewed by 7094
Abstract
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as [...] Read more.
Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
2540 KiB  
Review
Three-Dimensional Structural Aspects of Protein–Polysaccharide Interactions
by Masamichi Nagae and Yoshiki Yamaguchi
Int. J. Mol. Sci. 2014, 15(3), 3768-3783; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15033768 - 03 Mar 2014
Cited by 32 | Viewed by 9626
Abstract
Linear polysaccharides are typically composed of repeating mono- or disaccharide units and are ubiquitous among living organisms. Polysaccharide diversity arises from chain-length variation, branching, and additional modifications. Structural diversity is associated with various physiological functions, which are often regulated by cognate polysaccharide-binding proteins. [...] Read more.
Linear polysaccharides are typically composed of repeating mono- or disaccharide units and are ubiquitous among living organisms. Polysaccharide diversity arises from chain-length variation, branching, and additional modifications. Structural diversity is associated with various physiological functions, which are often regulated by cognate polysaccharide-binding proteins. Proteins that interact with linear polysaccharides have been identified or developed, such as galectins and polysaccharide-specific antibodies, respectively. Currently, data is accumulating on the three-dimensional structure of polysaccharide-binding proteins. These proteins are classified into two types: exo-type and endo-type. The former group specifically interacts with the terminal units of polysaccharides, whereas the latter with internal units. In this review, we describe the structural aspects of exo-type and endo-type protein-polysaccharide interactions. Further, we discuss the structural basis for affinity and specificity enhancement in the face of inherently weak binding interactions. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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Graphical abstract

402 KiB  
Review
Gram-Negative Flagella Glycosylation
by Susana Merino and Juan M. Tomás
Int. J. Mol. Sci. 2014, 15(2), 2840-2857; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms15022840 - 19 Feb 2014
Cited by 50 | Viewed by 9371
Abstract
Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now established that bacteria possess both N-linked and O-linked glycosylation pathways. Both glycosylation pathways can modify multiple proteins, [...] Read more.
Protein glycosylation had been considered as an eccentricity of a few bacteria. However, through advances in analytical methods and genome sequencing, it is now established that bacteria possess both N-linked and O-linked glycosylation pathways. Both glycosylation pathways can modify multiple proteins, flagellins from Archaea and Eubacteria being one of these. Flagella O-glycosylation has been demonstrated in many polar flagellins from Gram-negative bacteria and in only the Gram-positive genera Clostridium and Listeria. Furthermore, O-glycosylation has also been demonstrated in a limited number of lateral flagellins. In this work, we revised the current advances in flagellar glycosylation from Gram-negative bacteria, focusing on the structural diversity of glycans, the O-linked pathway and the biological function of flagella glycosylation. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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948 KiB  
Review
Boronic Acid-Based Approach for Separation and Immobilization of Glycoproteins and Its Application in Sensing
by Xiaojin Wang, Ning Xia and Lin Liu
Int. J. Mol. Sci. 2013, 14(10), 20890-20912; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms141020890 - 17 Oct 2013
Cited by 83 | Viewed by 14884
Abstract
Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols [...] Read more.
Glycoproteins influence a broad spectrum of biological processes including cell-cell interaction, host-pathogen interaction, or protection of proteins against proteolytic degradation. The analysis of their glyco-structures and concentration levels are increasingly important in diagnosis and proteomics. Boronic acids can covalently react with cis-diols in the oligosaccharide chains of glycoproteins to form five- or six-membered cyclic esters. Based on this interaction, boronic acid-based ligands and materials have attracted much attention in both chemistry and biology as the recognition motif for enrichment and chemo/biosensing of glycoproteins in recent years. In this work, we reviewed the progress in the separation, immobilization and detection of glycoproteins with boronic acid-functionalized materials and addressed its application in sensing. Full article
(This article belongs to the Special Issue Glycosylation and Glycoproteins)
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