ijms-logo

Journal Browser

Journal Browser

Special Issue "Protein Glycosylation in the Secretory Pathway: Variation, Biosynthesis and Function"

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

Deadline for manuscript submissions: 31 December 2019.

Special Issue Editors

Prof. Dr. Sabine Strahl
E-Mail Website
Guest Editor
Heidelberg University, Centre for Organismal Studies (COS), Department Glycobiology, Heidelberg, Germany
Interests: protein glycosylation; glycoproteins; glycosyltransferases; O-mannosyl glycans; endoplasmic reticulum
Prof. Dr. Bernd Lepenies
E-Mail Website
Guest Editor
University of Veterinary Medicine Hannover, Research Center for Emerging Infections and Zoonoses (RIZ), Hannover, Germany
Interests: protein glycosylation; lectins; C-type lectin receptors; innate immunity

Special Issue Information

Dear Colleagues,

 

    In the postgenomic and proteomic era, it is becoming increasingly clear that we cannot fully understand basic cell biology as well as the growth and development of complex multicellular organisms by exploring proteins, without considering the many possible modifications. Proteins that enter and pass through the secretory pathway receive glycans, a highly diverse, complex, and energy-demanding post-translational modification. More than nine different monosaccharides, which are either N-, O- or C-glycosidically linked to the polypeptide chain, already reflect the complexity of protein glycosylation. Protein-bound sugar moieties may be further extended by highly organized reactions, ultimately leading to a glycoproteome of immense variety and information content that is cell type-specific and may even vary depending on the condition of the cell (e.g., inflammation).
    Recent glycoproteomic and glycomic studies have clearly shown that the vast majority of proteins entering the secretory pathway are glycosylated. The glycan structures and glycosylation pattern are dynamically and differentially regulated during development as well as under certain pathological conditions. Glycosciences are undoubtedly experiencing a boom, as it is becoming more and more apparent that glycoproteins affect virtually all aspects of growth and development in the health and disease processes of eukaryotes.
    This Special Issue will cover a broad range of studies on diversity, biosynthesis, and the function of protein glycosylation in eukaryotes ranging from yeast to human disease models. Experimental papers, recent review articles, and commentaries are welcome.

 

Prof. Dr. Sabine Strahl
Prof. Dr. Bernd Lepenies
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 papers will be 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. 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. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • Glycosylation
  • N-glycosylation
  • O-glycosylation
  • Glypiation
  • Glycan
  • Glycomics
  • Glycoproteomics
  • Glycoprotein
  • Glycosyltransferase
  • Membrane protein
  • Dolichol
  • Lipid linked oligosaccharide
  • Sugar nucleotide transport
  • Endoplasmic reticulum
  • Golgi apparatus
  • ER protein quality control
  • ER associated protein degradation
  • Protein maturation
  • Cellular trafficking
  • Cell–cell interaction
  • Cell–matrix interaction
  • Congenital disorders of glycosylation
  • Dystroglycanopathy
  • Fungal pathogenicity
  • Innate immunity
  • Immunology
  • Cancer

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Open AccessArticle
Translational Regulation of Pmt1 and Pmt2 by Bfr1 Affects Unfolded Protein O-Mannosylation
Int. J. Mol. Sci. 2019, 20(24), 6220; https://doi.org/10.3390/ijms20246220 - 10 Dec 2019
Abstract
O-mannosylation is implicated in protein quality control in Saccharomyces cerevisiae due to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile [...] Read more.
O-mannosylation is implicated in protein quality control in Saccharomyces cerevisiae due to the attachment of mannose to serine and threonine residues of un- or misfolded proteins in the endoplasmic reticulum (ER). This process also designated as unfolded protein O-mannosylation (UPOM) that ends futile folding cycles and saves cellular resources is mainly mediated by protein O-mannosyltransferases Pmt1 and Pmt2. Here we describe a genetic screen for factors that influence O-mannosylation in yeast, using slow-folding green fluorescent protein (GFP) as a reporter. Our screening identifies the RNA binding protein brefeldin A resistance factor 1 (Bfr1) that has not been linked to O-mannosylation and ER protein quality control before. We find that Bfr1 affects O-mannosylation through changes in Pmt1 and Pmt2 protein abundance but has no effect on PMT1 and PMT2 transcript levels, mRNA localization to the ER membrane or protein stability. Ribosome profiling reveals that Bfr1 is a crucial factor for Pmt1 and Pmt2 translation thereby affecting unfolded protein O-mannosylation. Our results uncover a new level of regulation of protein quality control in the secretory pathway. Full article
Show Figures

Figure 1

Open AccessArticle
Increased Expression of Immature Mannose-Containing Glycoproteins and Sialic Acid in Aged Mouse Brains
Int. J. Mol. Sci. 2019, 20(24), 6118; https://doi.org/10.3390/ijms20246118 - 04 Dec 2019
Abstract
Aging represents the accumulation of changes in an individual over time, encompassing physical, psychological, and social changes. Posttranslational modifications of proteins such as glycosylation, including sialylation or glycation, are proposed to be involved in this process, since they modulate a variety of molecular [...] Read more.
Aging represents the accumulation of changes in an individual over time, encompassing physical, psychological, and social changes. Posttranslational modifications of proteins such as glycosylation, including sialylation or glycation, are proposed to be involved in this process, since they modulate a variety of molecular and cellular functions. In this study, we analyzed selected posttranslational modifications and the respective proteins on which they occur in young and old mouse brains. The expression of neural cell adhesion molecule (NCAM), receptor for advanced glycation endproducts (RAGE), as well as the carbohydrate-epitopes paucimannose and high-mannose, polysialic acid, and O-GlcNAc were examined. We demonstrated that mannose-containing glycans increased on glycoproteins in aged mouse brains and identified synapsin-1 as one major carrier of paucimannose in aged brains. In addition, we found an accumulation of so-called advanced glycation endproducts, which are generated by non-enzymatic reactions and interfere with protein function. Furthermore, we analyzed the expression of sialic acid and found also an increase during aging. Full article
Show Figures

Figure 1

Open AccessArticle
Inhibition of Dephosphorylation of Dolichyl Diphosphate Alters the Synthesis of Dolichol and Hinders Protein N-Glycosylation and Morphological Transitions in Candida albicans
Int. J. Mol. Sci. 2019, 20(20), 5067; https://doi.org/10.3390/ijms20205067 - 12 Oct 2019
Abstract
The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after [...] Read more.
The essential role of dolichyl phosphate (DolP) as a carbohydrate carrier during protein N-glycosylation is well established. The cellular pool of DolP is derived from de novo synthesis in the dolichol branch of the mevalonate pathway and from recycling of DolPP after each cycle of N-glycosylation, when the oligosaccharide is transferred from the lipid carrier to the protein and DolPP is released and then dephosphorylated. In Saccharomyces cerevisiae, the dephosphorylation of DolPP is known to be catalyzed by the Cwh8p protein. To establish the role of the Cwh8p orthologue in another distantly related yeast species, Candida albicans, we studied its mutant devoid of the CaCWH8 gene. A double Cacwh8∆/Cacwh8∆ strain was constructed by the URA-blaster method. As in S. cerevisiae, the mutant was impaired in DolPP recycling. This defect, however, was accompanied by an elevation of cis-prenyltransferase activity and higher de novo production of dolichols. Despite these compensatory changes, protein glycosylation, cell wall integrity, filamentous growth, and biofilm formation were impaired in the mutant. These results suggest that the defects are not due to the lack of DolP for the protein N-glycosylation but rather that the activity of oligosacharyltransferase could be inhibited by the excess DolPP accumulating in the mutant. Full article
Show Figures

Graphical abstract

Open AccessArticle
Membrane Topological Model of Glycosyltransferases of the GT-C Superfamily
Int. J. Mol. Sci. 2019, 20(19), 4842; https://doi.org/10.3390/ijms20194842 - 29 Sep 2019
Abstract
Glycosyltransferases that use polyisoprenol-linked donor substrates are categorized in the GT-C superfamily. In eukaryotes, they act in the endoplasmic reticulum (ER) lumen and are involved in N-glycosylation, glypiation, O-mannosylation, and C-mannosylation of proteins. We generated a membrane topology model of [...] Read more.
Glycosyltransferases that use polyisoprenol-linked donor substrates are categorized in the GT-C superfamily. In eukaryotes, they act in the endoplasmic reticulum (ER) lumen and are involved in N-glycosylation, glypiation, O-mannosylation, and C-mannosylation of proteins. We generated a membrane topology model of C-mannosyltransferases (DPY19 family) that concurred perfectly with the 13 transmembrane domains (TMDs) observed in oligosaccharyltransferases (STT3 family) structures. A multiple alignment of family members from diverse organisms highlighted the presence of only a few conserved amino acids between DPY19s and STT3s. Most of these residues were shown to be essential for DPY19 function and are positioned in luminal loops that showed high conservation within the DPY19 family. Multiple alignments of other eukaryotic GT-C families underlined the presence of similar conserved motifs in luminal loops, in all enzymes of the superfamily. Most GT-C enzymes are proposed to have an uneven number of TDMs with 11 (POMT, TMTC, ALG9, ALG12, PIGB, PIGV, and PIGZ) or 13 (DPY19, STT3, and ALG10) membrane-spanning helices. In contrast, PIGM, ALG3, ALG6, and ALG8 have 12 or 14 TMDs and display a C-terminal dilysine ER-retrieval motif oriented towards the cytoplasm. We propose that all members of the GT-C superfamily are evolutionary related enzymes with preserved membrane topology. Full article
Show Figures

Graphical abstract

Open AccessArticle
Exploring the N-Glycosylation Profile of Glycoprotein B from Human Cytomegalovirus Expressed in CHO and Nicotiana tabacum BY-2 Cells
Int. J. Mol. Sci. 2019, 20(15), 3741; https://doi.org/10.3390/ijms20153741 - 31 Jul 2019
Abstract
The ability to control the glycosylation pattern of recombinant viral glycoproteins represents a major prerequisite before their use as vaccines. The aim of this study consisted of expressing the large soluble ectodomain of glycoprotein B (gB) from Human Cytomegalovirus (HMCV) in Nicotiana tabacum [...] Read more.
The ability to control the glycosylation pattern of recombinant viral glycoproteins represents a major prerequisite before their use as vaccines. The aim of this study consisted of expressing the large soluble ectodomain of glycoprotein B (gB) from Human Cytomegalovirus (HMCV) in Nicotiana tabacum Bright Yellow-2 (BY-2) suspension cells and of comparing its glycosylation profile with that of gB produced in Chinese hamster ovary (CHO) cells. gB was secreted in the BY-2 culture medium at a concentration of 20 mg/L and directly purified by ammonium sulfate precipitation and size exclusion chromatography. We then measured the relative abundance of N-glycans present on 15 (BY-2) and 17 (CHO) out of the 18 N-sites by multienzymatic proteolysis and mass spectrometry. The glycosylation profile differed at each N-site, some sites being occupied exclusively by oligomannosidic type N-glycans and others by complex N-glycans processed in some cases with additional Lewis A structures (BY-2) or with beta-1,4-galactose and sialic acid (CHO). The profiles were strikingly comparable between BY-2- and CHO-produced gB. These results suggest a similar gB conformation when glycoproteins are expressed in plant cells as site accessibility influences the glycosylation profile at each site. These data thus strengthen the BY-2 suspension cultures as an alternative expression system. Full article
Show Figures

Graphical abstract

Open AccessArticle
Poly-Saturated Dolichols from Filamentous Fungi Modulate Activity of Dolichol-Dependent Glycosyltransferase and Physical Properties of Membranes
Int. J. Mol. Sci. 2019, 20(12), 3043; https://doi.org/10.3390/ijms20123043 - 21 Jun 2019
Abstract
Mono-saturated polyprenols (dolichols) have been found in almost all Eukaryotic cells, however, dolichols containing additional saturated bonds at the ω-end, have been identified in A. fumigatus and A. niger. Here we confirm using an LC-ESI-QTOF-MS analysis, that poly-saturated dolichols are abundant in [...] Read more.
Mono-saturated polyprenols (dolichols) have been found in almost all Eukaryotic cells, however, dolichols containing additional saturated bonds at the ω-end, have been identified in A. fumigatus and A. niger. Here we confirm using an LC-ESI-QTOF-MS analysis, that poly-saturated dolichols are abundant in other filamentous fungi, Trichoderma reesei, A. nidulans and Neurospora crassa, while the yeast Saccharomyces cerevisiae only contains the typical mono-saturated dolichols. We also show, using differential scanning calorimetry (DSC) and fluorescence anisotropy of 1,6-diphenyl-l,3,5-hexatriene (DPH) that the structure of dolichols modulates the properties of membranes and affects the functioning of dolichyl diphosphate mannose synthase (DPMS). The activity of this enzyme from T. reesei and S. cerevisiae was strongly affected by the structure of dolichols. Additionally, the structure of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) model membranes was more strongly disturbed by the poly-saturated dolichols from Trichoderma than by the mono-saturated dolichols from yeast. By comparing the lipidome of filamentous fungi with that from S. cerevisiae, we revealed significant differences in the PC/PE ratio and fatty acids composition. Filamentous fungi differ from S. cerevisiae in the lipid composition of their membranes and the structure of dolichols. The structure of dolichols profoundly affects the functioning of dolichol-dependent enzyme, DPMS. Full article
Show Figures

Figure 1

Review

Jump to: Research

Open AccessReview
Oligosaccharyltransferase: A Gatekeeper of Health and Tumor Progression
Int. J. Mol. Sci. 2019, 20(23), 6074; https://doi.org/10.3390/ijms20236074 - 02 Dec 2019
Abstract
Oligosaccharyltransferase (OST) is a multi-span membrane protein complex that catalyzes the addition of glycans to selected Asn residues within nascent polypeptides in the lumen of the endoplasmic reticulum. This process, termed N-glycosylation, is a fundamental post-translational protein modification that is involved in the [...] Read more.
Oligosaccharyltransferase (OST) is a multi-span membrane protein complex that catalyzes the addition of glycans to selected Asn residues within nascent polypeptides in the lumen of the endoplasmic reticulum. This process, termed N-glycosylation, is a fundamental post-translational protein modification that is involved in the quality control, trafficking of proteins, signal transduction, and cell-to-cell communication. Given these crucial roles, N-glycosylation is essential for homeostasis at the systemic and cellular levels, and a deficiency in genes that encode for OST subunits often results in the development of complex genetic disorders. A growing body of evidence has also demonstrated that the expression of OST subunits is cell context-dependent and is frequently altered in malignant cells, thus contributing to tumor cell survival and proliferation. Importantly, a recently developed inhibitor of OST has revealed this enzyme as a potential target for the treatment of incurable drug-resistant tumors. This review summarizes our current knowledge regarding the functions of OST in the light of health and tumor progression, and discusses perspectives on the clinical relevance of inhibiting OST as a tumor treatment. Full article
Show Figures

Figure 1

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Mucosal glycosylation as a molecular player in colitis-associated colorectal cancer

Salome Pinho

Colitis-associated Cancer (CAC) is a major complication of Ulcerative Colitis remaining an important clinical challenge in terms of diagnosis and prognosis. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated with colon inflammation and with colorectal cancer development. In this review, we discuss the major molecular drivers of CAC pathogenesis, highlighting the role of glycans in the regulation of intestinal inflammation and its progression to CAC.

 

Structure and function of glycosyltransferases involved in N-glycan maturation

Masamichi Nagae, Yasuhiko Kizuka, Naoyuki Taniguchi and Yoshiki Yamaguchi

Short abstract: Glycosylation is the most ubiquitous post translational modifications in eukaryotes. N-glycan is attached to nascent glycoprotein and processed and matured by various glycosidases and glycosyltransferases during protein transport. Alternations of N-glycan structure play crucial roles in various physiological and pathological events including cancer progression. Especially, the formation of N-glycan branches catalyzed by specific N-acetylglucosaminyltransferases such as GnT-III, GnT-IVs, GnT-V, and GnT-IX and a fucosyltransferase, FUT8, regulates the functions of target glycoproteins. Recent progresses of structural analysis on these glycosyltransferases have provided insights into substrate recognition and catalytic reaction mechanisms. In this review, the structure-function relationships of these enzymes are discussed.

Back to TopTop