Advances in understanding N-glycosylation structure, function, and regulation in health and disease

Esmail, Sally; Manolson, Morris F.

doi:10.1016/j.ejcb.2021.151186

Cited by 79 publications

(63 citation statements)

References 92 publications

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“…Glycosylation is an important posttranslational modification involving N-glycosylation ( 35 ) and O-glycosylation ( 36 ) and is significantly related to a variety of pathological and physiological processes. Previous studies have found that N-glycosylation is associated with the function of many ion channels, and an association between the dysfunction of glycosylation in potassium channels and long QT syndrome was observed ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Zheng

Chen

Liu

et al. 2022

Front. Cardiovasc. Med.

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BackgroundThe immune system significantly participates in the pathologic process of atrial fibrillation (AF). However, the molecular mechanisms underlying this participation are not completely explained. The current research aimed to identify critical genes and immune cells that participate in the pathologic process of AF.MethodsCIBERSORT was utilized to reveal the immune cell infiltration pattern in AF patients. Meanwhile, weighted gene coexpression network analysis (WGCNA) was utilized to identify meaningful modules that were significantly correlated with AF. The characteristic genes correlated with AF were identified by the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithm.ResultsIn comparison to sinus rhythm (SR) individuals, we observed that fewer activated mast cells and regulatory T cells (Tregs), as well as more gamma delta T cells, resting mast cells, and M2 macrophages, were infiltrated in AF patients. Three significant modules (pink, red, and magenta) were identified to be significantly associated with AF. Gene enrichment analysis showed that all 717 genes were associated with immunity- or inflammation-related pathways and biological processes. Four hub genes (GALNT16, HTR2B, BEX2, and RAB8A) were revealed to be significantly correlated with AF by the SVM-RFE algorithm and LASSO logistic regression. qRT–PCR results suggested that compared to the SR subjects, AF patients exhibited significantly reduced BEX2 and GALNT16 expression, as well as dramatically elevated HTR2B expression. The AUC measurement showed that the diagnostic efficiency of BEX2, HTR2B, and GALNT16 in the training set was 0.836, 0.883, and 0.893, respectively, and 0.858, 0.861, and 0.915, respectively, in the validation set.ConclusionsThree novel genes, BEX2, HTR2B, and GALNT16, were identified by WGCNA combined with machine learning, which provides potential new therapeutic targets for the early diagnosis and prevention of AF.

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Section: Discussionmentioning

confidence: 99%

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Zheng

Chen

Liu

et al. 2022

Front. Cardiovasc. Med.

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“…It is widely known that N-linked protein glycosylation is an important cotranslational and post-translational modification in biology, playing an essential part in development, organ specific function and disease ( Zielinska et al, 2010 ; Esmail and Manolson, 2021 ). Tumor-related glycosylation alterations are connected with tumor progression, malignant transformation and immune evasion ( Rodrigues et al, 2018 ; Bindeman and Fingleton, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2

Cao

Meng

Shao

et al. 2022

Front. Mol. Biosci.

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Glycosylation inhibition has great potential in cancer treatment. However, the corresponding cellular response, protein expression and glycosylation changes remain unclear. As a cell-permeable small-molecule inhibitor with reduced cellular toxicity, N-linked glycosylation inhibitor-1 (NGI-1) has become a great approach to regulate glycosylation in mammalian cells. Here for the first time, we applied a nascent proteomic method to investigate the effect of NGI-1 in hepatocellular carcinoma (HCC) cell line. Besides, hydrophilic interaction liquid chromatography (HILIC) was adopted for the enrichment of glycosylated peptides. Glycoproteomic analysis revealed the abundance of glycopeptides from LAMP2, NICA, and CEIP2 was significantly changed during NGI-1 treatment. Moreover, the alterations of LAMP2 site-specific intact N-glycopeptides were comprehensively assessed. NGI-1 treatment also led to the inhibition of Cathepsin D maturation and the induction of autophagy. In summary, we provided evidence that NGI-1 repressed the expression of glycosylated LAMP2 accompanied with the occurrence of lysosomal defects and autophagy.

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“…Sequence analysis showed that c.1325A > G in OCA2 may disrupt a putative N-linked glycosylation site Asn 442 that has also been predicted as a glycosylation site on the website https://www.uniprot.org/uniprot/Q04671 . N-linked glycosylation is important in quality control, stability, and function of glycoproteins such as trafficking or gating kinetics of channel protein, and the sequon Asn-X-Thr/Ser-X is a key determinant in the efficiency of glycosylation ( Esmail and Manolson, 2021 ). The variant at Val 443 adjacent to Asn 442 has recurred in European OCA ( Hutton and Spritz, 2008 ; Lasseaux et al, 2018 ; Marti et al, 2018 ) and is frequently reported in Chinese OCA ( Figure 3 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of 12 OCA Cases in Chinese Population and Two Novel Variants

et al. 2022

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OCA (oculocutaneous albinism) refers to a group of heterogeneous congenital disorders of which the common manifestations are variable degrees of cutaneous hypopigmentation and significant visual impairment, including poor visual acuity, photophobia, and nystagmus. Molecular analysis may elucidate its pathogenesis and be in favor of accurate diagnosis. High-throughput sequencing and Sanger sequencing were performed to detect mutational alleles and in silico analysis was performed for prediction of variant pathogenicity. Ten TYR-related and two OCA2-related patients were identified with 16 different variants with potential pathogenicity. Two novel missense variants [TYR: c.623T > G, p(Leu208Arg) and OCA2: c.1325A > G, p(Asn442Ser)] are identified in this study, and three OCA cases are reported for the first time in Chinese population based on their associated variants. Analysis of crystal structures of TYR ortholog and its paralog TYRP1 suggests that the substitution of Leu208 may have an impact on protein stability. This study may facilitate OCA diagnosis by expanding the mutational spectrum of TYR and OCA2 as well as further basic studies about these two genes.

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Advances in understanding N-glycosylation structure, function, and regulation in health and disease

Cited by 79 publications

References 92 publications

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Integrative identification of immune-related key genes in atrial fibrillation using weighted gene coexpression network analysis and machine learning

Nascent Glycoproteome Reveals That N-Linked Glycosylation Inhibitor-1 Suppresses Expression of Glycosylated Lysosome-Associated Membrane Protein-2

Identification of 12 OCA Cases in Chinese Population and Two Novel Variants

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