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Cells
Special Issues
Sugars on Cell Surfaces and Their Biological Purposes
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Sugars on Cell Surfaces and Their Biological Purposes

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 48102

Special Issue Editors

Dr. Sebastian P. Galuska

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Guest Editor
Leibniz Institute for Farm Animal Biology (FBN), Institute of Reproductive Biology, Wilhelm-Stahl-Allee 2, 18196 Dummerstorf, Germany
Interests: sialic acids; polysialic acid; glycoimmunology; siglecs; extracellular traps; innate immune system
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Rüdiger Horstkorte

E-Mail Website
Guest Editor
Institut für Physiologische Chemie Medizinische Fakultät Martin-Luther-Universität Halle-Wittenberg, University of Halle-Wittenberg, Hollystr.1, 06114 Halle (Saale), Germany
Interests: cell adhesion; posttranslational modifications; biochemistry, genetics and molecular biology neuroscience chemistry medicine chemical engineering agricultural and biological sciences immunology and microbiology computer science pharmacology, toxicology and pharmaceutic

Special Issue Information

Dear Colleagues,

Every cell is surrounded by a plasma membrane, which separates the cell from the extracellular environment and controls the exchange of substances. The outer leaflet of this plasma membrane contains numerous glycosylated proteins and lipids. This dense meshwork of glycoconjugates forms the so-called cellular glycocalyx. Since the glycans (sugars) of the cell surface reach far out into the extracellular space, they directly influence cellular processes, such as cell recognition, signal transduction or cell migration.

The aim of this Special Issue is to enlighten the role of these sugars in all aspects of physiological or pathophysiological mechanisms. We are looking for cutting-edge research demonstrating the role of sugars on the cell surface.

Topics of interest may include:

  • Glyco-engineering of cell surfaces
  • Non-enzymatic glycation of cell surface receptors
  • The role of glycans during development
  • Glycans and cancer
  • Neuroglycobiology
  • Glycoimmunology
  • Glycan mediated host−pathogen interactions

Articles will be peer-reviewed and published in the open access journal Cells (Impact Factor 5.656, ISSN 2073-4409). We look forward to your contributions.

Dr. Sebastian P. Galuska
Prof. Dr. Rüdiger Horstkorte
Guest Editors

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells 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 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Further information on MDPI's Special Issue polices can be found here.

Published Papers (8 papers)

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Research

Jump to: Review

21 pages, 3296 KiB  
Article
Role of Sialyl-O-Acetyltransferase CASD1 on GD2 Ganglioside O-Acetylation in Breast Cancer Cells
by Sumeyye Cavdarli, Larissa Schröter, Malena Albers, Anna-Maria Baumann, Dorothée Vicogne, Jean-Marc Le Doussal, Martina Mühlenhoff, Philippe Delannoy and Sophie Groux-Degroote
Cells 2021, 10(6), 1468; https://doi.org/10.3390/cells10061468 - 11 Jun 2021
Cited by 11 | Viewed by 4289
Abstract
The O-acetylated form of GD2, almost exclusively expressed in cancerous tissues, is considered to be a promising therapeutic target for neuroectoderm-derived tumors, especially for breast cancer. Our recent data have shown that 9-O-acetylated GD2 (9-OAcGD2) is the major [...] Read more.
The O-acetylated form of GD2, almost exclusively expressed in cancerous tissues, is considered to be a promising therapeutic target for neuroectoderm-derived tumors, especially for breast cancer. Our recent data have shown that 9-O-acetylated GD2 (9-OAcGD2) is the major O-acetylated ganglioside species in breast cancer cells. In 2015, Baumann et al. proposed that Cas 1 domain containing 1 (CASD1), which is the only known human sialyl-O-acetyltransferase, plays a role in GD3 O-acetylation. However, the mechanisms of ganglioside O-acetylation remain poorly understood. The aim of this study was to determine the involvement of CASD1 in GD2 O-acetylation in breast cancer. The role of CASD1 in OAcGD2 synthesis was first demonstrated using wild type CHO and CHOΔCasd1 cells as cellular models. Overexpression using plasmid transfection and siRNA strategies was used to modulate CASD1 expression in SUM159PT breast cancer cell line. Our results showed that OAcGD2 expression was reduced in SUM159PT that was transiently depleted for CASD1 expression. Additionally, OAcGD2 expression was increased in SUM159PT cells transiently overexpressing CASD1. The modulation of CASD1 expression using transient transfection strategies provided interesting insights into the role of CASD1 in OAcGD2 and OAcGD3 biosynthesis, and it highlights the importance of further studies on O-acetylation mechanisms. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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12 pages, 3942 KiB  
Article
The Loss of Polysialic Acid Impairs the Contractile Phenotype of Peritubular Smooth Muscle Cells in the Postnatal Testis
by Nadim E. Hachem, Luisa Humpfle, Peter Simon, Miriam Kaese, Birgit Weinhold, Juliane Günther, Sebastian P. Galuska and Ralf Middendorff
Cells 2021, 10(6), 1347; https://doi.org/10.3390/cells10061347 - 29 May 2021
Cited by 3 | Viewed by 3324
Abstract
In the testis, the germinal epithelium of seminiferous tubules is surrounded by contractile peritubular cells, which are involved in sperm transport. Interestingly, in postnatal testis, polysialic acid (polySia), which is also an essential player for the development of the brain, was observed around [...] Read more.
In the testis, the germinal epithelium of seminiferous tubules is surrounded by contractile peritubular cells, which are involved in sperm transport. Interestingly, in postnatal testis, polysialic acid (polySia), which is also an essential player for the development of the brain, was observed around the tubules. Western blotting revealed a massive decrease of polySia from postnatal day 1 towards puberty, together with a fundamental reduction of the net-like intertubular polySia. Using polysialyltransferase knockout mice, we investigated the consequences of the loss of polySia in the postnatal testis. Compared to postnatal wild-type animals, polySia knockouts showed slightly reduced smooth muscle actin (SMA) immunostaining of peritubular smooth muscle cells (SMCs), while calponin, marking more differentiated SMCs, dramatically decreased. In contrast, testicular SMA and calponin immunostaining remained unchanged in vascular SMCs in all genotypes. In addition, the cGMP-dependent protein kinase PKG I, a key enzyme of SMC relaxation, was nearly undetectable in the peritubular SMCs. Cell proliferation in the peritubular layer increased significantly in the knockouts, as shown by proliferating cell nuclear anti (PCNA) staining. Taken together, in postnatal testis, the absence of polySia resulted in an impaired differentiation of peritubular, but not vascular, SMCs to a more synthetic phenotype. Thus, polySia might influence the maintenance of a differentiated phenotype of non-vascular SMCs. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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17 pages, 6318 KiB  
Article
Glycoengineering Human Neural and Adipose Stem Cells with Novel Thiol-Modified N-Acetylmannosamine (ManNAc) Analogs
by Jian Du, Christian Agatemor, Christopher T. Saeui, Rahul Bhattacharya, Xiaofeng Jia and Kevin J. Yarema
Cells 2021, 10(2), 377; https://doi.org/10.3390/cells10020377 - 12 Feb 2021
Cited by 9 | Viewed by 3116
Abstract
This report describes novel thiol-modified N-acetylmannosamine (ManNAc) analogs that extend metabolic glycoengineering (MGE) applications of Ac5ManNTGc, a non-natural monosaccharide that metabolically installs the thio-glycolyl of sialic acid into human glycoconjugates. We previously found that Ac5ManNTGc elicited non-canonical activation [...] Read more.
This report describes novel thiol-modified N-acetylmannosamine (ManNAc) analogs that extend metabolic glycoengineering (MGE) applications of Ac5ManNTGc, a non-natural monosaccharide that metabolically installs the thio-glycolyl of sialic acid into human glycoconjugates. We previously found that Ac5ManNTGc elicited non-canonical activation of Wnt signaling in human embryoid body derived (hEBD) cells but only in the presence of a high affinity, chemically compatible scaffold. Our new analogs Ac5ManNTProp and Ac5ManNTBut overcome the requirement for a complementary scaffold by displaying thiol groups on longer, N-acyl linker arms, thereby presumably increasing their ability to interact and crosslink with surrounding thiols. These new analogs showed increased potency in human neural stem cells (hNSCs) and human adipose stem cells (hASCs). In the hNSCs, Ac5ManNTProp upregulated biochemical endpoints consistent with Wnt signaling in the absence of a thiol-reactive scaffold. In the hASCs, both Ac5ManNTProp and Ac5ManNTBut suppressed adipogenic differentiation, with Ac5ManNTBut providing a more potent response, and they did not interfere with differentiation to a glial lineage (Schwann cells). These results expand the horizon for using MGE in regenerative medicine by providing new tools (Ac5ManNTProp and Ac5ManNTBut) for manipulating human stem cells. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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15 pages, 4469 KiB  
Article
Characterization of the Polysialylation Status in Ovaries of the Salmonid Fish Coregonus maraena and the Percid Fish Sander lucioperca
by Marzia Tindara Venuto, Joan Martorell-Ribera, Ralf Bochert, Anne Harduin-Lepers, Alexander Rebl and Sebastian Peter Galuska
Cells 2020, 9(11), 2391; https://doi.org/10.3390/cells9112391 - 31 Oct 2020
Cited by 6 | Viewed by 2683
Abstract
In vertebrates, the carbohydrate polymer polysialic acid (polySia) is especially well known for its essential role during neuronal development, regulating the migration and proliferation of neural precursor cells, for instance. Nevertheless, sialic acid polymers seem to be regulatory elements in other physiological systems, [...] Read more.
In vertebrates, the carbohydrate polymer polysialic acid (polySia) is especially well known for its essential role during neuronal development, regulating the migration and proliferation of neural precursor cells, for instance. Nevertheless, sialic acid polymers seem to be regulatory elements in other physiological systems, such as the reproductive tract. Interestingly, trout fish eggs have polySia, but we know little of its cellular distribution and role during oogenesis. Therefore, we localized α2,8-linked N-acetylneuraminic acid polymers in the ovaries of Coregonus maraena by immunohistochemistry and found that prevalent clusters of oogonia showed polySia signals on their surfaces. Remarkably, the genome of this salmonid fish contains two st8sia2 genes and one st8sia4 gene, that is, three polysialyltransferases. The expression analysis revealed that for st8sia2-r2, 60 times more mRNA was present than st8sia2-r1 and st8sia4. To compare polysialylation status regarding various polySiaT configurations, we performed a comparable analysis in Sander lucioperca. The genome of this perciform fish contains only one st8sia2 and no st8sia4 gene. Here, too, clusters of oogonia showed polysialylated cell surfaces, and we detected high mRNA values for st8sia2. These results suggest that in teleosts, polySia is involved in the cellular processes of oogonia during oogenesis. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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Review

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21 pages, 4108 KiB  
Review
Siglec Ligands
by Anabel Gonzalez-Gil and Ronald L. Schnaar
Cells 2021, 10(5), 1260; https://doi.org/10.3390/cells10051260 - 20 May 2021
Cited by 62 | Viewed by 9405
Abstract
A dense and diverse array of glycans on glycoproteins and glycolipids decorate all cell surfaces. In vertebrates, many of these carry sialic acid, in a variety of linkages and glycan contexts, as their outermost sugar moiety. Among their functions, glycans engage complementary glycan [...] Read more.
A dense and diverse array of glycans on glycoproteins and glycolipids decorate all cell surfaces. In vertebrates, many of these carry sialic acid, in a variety of linkages and glycan contexts, as their outermost sugar moiety. Among their functions, glycans engage complementary glycan binding proteins (lectins) to regulate cell physiology. Among the glycan binding proteins are the Siglecs, sialic acid binding immunoglobulin-like lectins. In humans, there are 14 Siglecs, most of which are expressed on overlapping subsets of immune system cells. Each Siglec engages distinct, endogenous sialylated glycans that initiate signaling programs and regulate cellular responses. Here, we explore the emerging science of Siglec ligands, including endogenous sialoglycoproteins and glycolipids and synthetic sialomimetics. Knowledge in this field promises to reveal new molecular pathways controlling cell physiology and new opportunities for therapeutic intervention. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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31 pages, 2363 KiB  
Review
Role of Glycans on Key Cell Surface Receptors That Regulate Cell Proliferation and Cell Death
by Yin Gao, Xue Luan, Jacob Melamed and Inka Brockhausen
Cells 2021, 10(5), 1252; https://doi.org/10.3390/cells10051252 - 19 May 2021
Cited by 27 | Viewed by 7670
Abstract
Cells undergo proliferation and apoptosis, migration and differentiation via a number of cell surface receptors, most of which are heavily glycosylated. This review discusses receptor glycosylation and the known roles of glycans on the functions of receptors expressed in diverse cell types. We [...] Read more.
Cells undergo proliferation and apoptosis, migration and differentiation via a number of cell surface receptors, most of which are heavily glycosylated. This review discusses receptor glycosylation and the known roles of glycans on the functions of receptors expressed in diverse cell types. We included growth factor receptors that have an intracellular tyrosine kinase domain, growth factor receptors that have a serine/threonine kinase domain, and cell-death-inducing receptors. N- and O-glycans have a wide range of functions including roles in receptor conformation, ligand binding, oligomerization, and activation of signaling cascades. A better understanding of these functions will enable control of cell survival and cell death in diseases such as cancer and in immune responses. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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19 pages, 1238 KiB  
Review
Sialic Acids and Their Influence on Human NK Cell Function
by Philip Rosenstock and Thomas Kaufmann
Cells 2021, 10(2), 263; https://doi.org/10.3390/cells10020263 - 29 Jan 2021
Cited by 19 | Viewed by 5605
Abstract
Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and [...] Read more.
Sialic acids are sugars with a nine-carbon backbone, present on the surface of all cells in humans, including immune cells and their target cells, with various functions. Natural Killer (NK) cells are cells of the innate immune system, capable of killing virus-infected and tumor cells. Sialic acids can influence the interaction of NK cells with potential targets in several ways. Different NK cell receptors can bind sialic acids, leading to NK cell inhibition or activation. Moreover, NK cells have sialic acids on their surface, which can regulate receptor abundance and activity. This review is focused on how sialic acids on NK cells and their target cells are involved in NK cell function. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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25 pages, 1746 KiB  
Review
Glycosylation of Cancer Extracellular Vesicles: Capture Strategies, Functional Roles and Potential Clinical Applications
by Álvaro M. Martins, Cátia C. Ramos, Daniela Freitas and Celso A. Reis
Cells 2021, 10(1), 109; https://doi.org/10.3390/cells10010109 - 8 Jan 2021
Cited by 80 | Viewed by 9896
Abstract
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic [...] Read more.
Glycans are major constituents of extracellular vesicles (EVs). Alterations in the glycosylation pathway are a common feature of cancer cells, which gives rise to de novo or increased synthesis of particular glycans. Therefore, glycans and glycoproteins have been widely used in the clinic as both stratification and prognosis cancer biomarkers. Interestingly, several of the known tumor-associated glycans have already been identified in cancer EVs, highlighting EV glycosylation as a potential source of circulating cancer biomarkers. These particles are crucial vehicles of cell–cell communication, being able to transfer molecular information and to modulate the recipient cell behavior. The presence of particular glycoconjugates has been described to be important for EV protein sorting, uptake and organ-tropism. Furthermore, specific EV glycans or glycoproteins have been described to be able to distinguish tumor EVs from benign EVs. In this review, the application of EV glycosylation in the development of novel EV detection and capture methodologies is discussed. In addition, we highlight the potential of EV glycosylation in the clinical setting for both cancer biomarker discovery and EV therapeutic delivery strategies. Full article
(This article belongs to the Special Issue Sugars on Cell Surfaces and Their Biological Purposes)
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