Mucin-Type O-GalNAc Glycosylation in Health and Disease

Bagdonaite, Ieva; Pallesen, Emil M.H.; Nielsen, Mathias I.; Bennett, Eric; Wandall, Hans H.

doi:10.1007/978-3-030-70115-4_2

Cited by 26 publications

(18 citation statements)

References 321 publications

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“…Mucins are a large family of high molecular weight proteins, which are composed of amino acids (such as glycine, serine, and threonine) ( Feller et al, 1990 ; Chakraborty et al, 2011 ; Ramsey et al, 2016 ; Bansil and Turner, 2018 ). And, Mucin O-glycosylation is a common covalent modification of serine and threonine residues of glycoproteins ( Van den Steen et al, 1998 ; Bagdonaite et al, 2021 ). Therefore, our results indicate that heat stress may affect the synthesis of mucins via amino acid metabolic and O-glycan biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Heat Stress Weakens the Skin Barrier Function in Sturgeon by Decreasing Mucus Secretion and Disrupting the Mucosal Microbiota

Yang

Tan

et al. 2022

Front. Microbiol.

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Heat stress induced by global warming has damaged the well-being of aquatic animals. The skin tissue plays a crucial role as a defense barrier to protect organism, however, little is known about the effect of heat stress on fish skin, particularly in cold-water fish species. Here, we investigated the effects of mild heat stress (24°C, MS) and high heat stress (28°C, HS) on Siberian sturgeon skin using RNA-seq, histological observation, and microbial diversity analysis. In RNA-seq, 8,819 differentially expressed genes (DEGs) in MS vs. C group and 12,814 DEGs in HS vs. C group were acquired, of which the MS vs. C and HS vs. C groups shared 3,903 DEGs, but only 1,652 DEGs were successfully annotated. The shared DEGs were significantly enriched in pathways associating with mucins synthesis. Histological observation showed that the heat stresses significantly reduced the number of skin mucous cells and induced the damages of epidermis. The microbial diversity analysis elicited that heat stress markedly disrupted the diversity and abundance of skin microbiota by increasing of potential pathogens (Vibrionimonas, Mesorhizobium, and Phyllobacterium) and decreasing of probiotics (Bradyrhizobium and Methylovirgula). In conclusion, this study reveals that heat stress causes adverse effects on sturgeon skin, reflecting in decreasing the mucus secretion and disordering the mucosal microbiota, which may contribute to develop the preventive strategy for heat stress caused by global warming.

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Section: Discussionmentioning

confidence: 99%

Heat Stress Weakens the Skin Barrier Function in Sturgeon by Decreasing Mucus Secretion and Disrupting the Mucosal Microbiota

Yang

Tan

et al. 2022

Front. Microbiol.

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Section: Discussionmentioning

confidence: 99%

“…Regulation of O-glycan initiation by competing GalNAc-Ts is not completely understood, and while there is no consensus sequence for O-glycosylation in general, or the individual isoforms, there are slight differences in amino acid context preference by the individual catalytic domains (Bagdonaite et al, 2021; de Las Rivas et al, 2019). Furthermore, most GalNAc-Ts are capable of long-range follow-up due to positioning by the lectin domain recognizing distant already glycosylated sites, where varying linker length between the two domains determines the range (de Las Rivas et al, 2017; Fritz et al, 2004; Pedersen et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Isoform-specific O-glycosylation dictates Ebola virus infectivity

Bagdonaite

Abdurahman

Mirandola

et al. 2022

Preprint

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Ebola virus glycoprotein is one of the most heavily O-glycosylated viral envelope glycoproteins. The glycoprotein possesses a large mucin-like domain responsible for the cytopathic effect on infected cells, yet its structure or potential role in early entry events is poorly defined. To understand the importance of elongated O-glycans and the individual O-glycosylation sites for viral infectivity, we performed a comprehensive characterization of site-specific glycosylation governed by the three key GalNAc-transferases, GalNAc-T1, -T2, and -T3, initiating O-glycan biosynthesis. Using TMT isobaric labelling we performed quantitative differential O-glycoproteomics on proteins produced in wild type HEK293 cells and cell lines ablated for each of the three GalNAc-Ts, as well as compared it to patterns on wild type virus-like particles. In total we found 38 and 41 O-glycosites on virus like particle-derived and recombinant GP, respectively, with well correlated sites and site-specific structures. Examination of the isoform-specific glycosylation demonstrate selective initiation of a subset of O-glycosites by each enzyme, with GalNAc-T1 having the largest contribution. We next demonstrate that O-linked glycan truncation and perturbed initiation retarded the production of viral particles and decreased infectivity of progeny virus. This work represents a comprehensive site-specific analysis of EBOV GP and sheds light on differential regulation of EBOV GP glycosylation initiated by host GalNAc-Ts. Together with the effect on viral propagation it opens prospective avenues for tailored intervention approaches and means for modulating immunogen O-glycan density.

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“…The generalization of these approaches has been greatly facilitated by the pioneer work at Wandall’s lab [ 136 , 138 , 140 , 141 ], which delivered a validated gRNA library for CRISPR/Cas9 targeting of the human glycosyltransferase genome [ 142 ]. This technology has been used to generate a wide number of different cancer cells expressing immature O -GalNAc glycosylation [ 143 – 145 ] which, to great extent, support our current knowledge on their role in heath and disease [ 146 ]. However, cellular glycoengineering for modulation of protein N - and O -glycosylation is being explored beyond its functional dimension, constituting an important tool for producing therapeutic glycoproteins [ 147 , 148 ] (Fig.…”

Section: Models For Cancer Glycobiology and Glycoimmunologymentioning

confidence: 99%

A roadmap for translational cancer glycoimmunology at single cell resolution

Peixoto

Miranda

Santos

et al. 2022

J Exp Clin Cancer Res

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Cancer cells can evade immune responses by exploiting inhibitory immune checkpoints. Immune checkpoint inhibitor (ICI) therapies based on anti-CTLA-4 and anti-PD-1/PD-L1 antibodies have been extensively explored over the recent years to unleash otherwise compromised anti-cancer immune responses. However, it is also well established that immune suppression is a multifactorial process involving an intricate crosstalk between cancer cells and the immune systems. The cancer glycome is emerging as a relevant source of immune checkpoints governing immunosuppressive behaviour in immune cells, paving an avenue for novel immunotherapeutic options. This review addresses the current state-of-the-art concerning the role played by glycans controlling innate and adaptive immune responses, while shedding light on available experimental models for glycoimmunology. We also emphasize the tremendous progress observed in the development of humanized models for immunology, the paramount contribution of advances in high-throughput single-cell analysis in this context, and the importance of including predictive machine learning algorithms in translational research. This may constitute an important roadmap for glycoimmunology, supporting careful adoption of models foreseeing clinical translation of fundamental glycobiology knowledge towards next generation immunotherapies.

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Mucin-Type O-GalNAc Glycosylation in Health and Disease

Cited by 26 publications

References 321 publications

Heat Stress Weakens the Skin Barrier Function in Sturgeon by Decreasing Mucus Secretion and Disrupting the Mucosal Microbiota

Heat Stress Weakens the Skin Barrier Function in Sturgeon by Decreasing Mucus Secretion and Disrupting the Mucosal Microbiota

Isoform-specific O-glycosylation dictates Ebola virus infectivity

A roadmap for translational cancer glycoimmunology at single cell resolution

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