Cell-type-specific labeling and profiling of glycans in living mice

Fan, Xinqi; Song, Qitao; Sun, De‐en; Hao, Yi; Wang, Jingyang; Wang, Chunting; Chen, Xing

doi:10.1038/s41589-022-01016-4

Cited by 32 publications

(23 citation statements)

References 44 publications

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“…Second, directly incorporating glycans in the analysis will give insight into cell-type-specific glycosylation sites and possibly glycan structures to add another dimension to proteome profiling. Chen and colleagues have engineered the AGX1 splice form AGX2 to accept an alkyne-tagged analogue of GlcNAc, achieving cell-specific glycoproteome tagging in vivo with focus on intracellular O-GlcNAc glycans 41 . While chemical tagging of intracellular O-GlcNAc glycans by BOCTAG is likely, we have focused on incorporation into cell surface glycans, including N-linked and, by virtue of engineered GTs, O-GalNAc glycans.…”

Section: Discussionmentioning

confidence: 99%

Cell-specific bioorthogonal tagging of glycoproteins

et al. 2022

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Altered glycoprotein expression is an undisputed corollary of cancer development. Understanding these alterations is paramount but hampered by limitations underlying cellular model systems. For instance, the intricate interactions between tumour and host cannot be adequately recapitulated in monoculture of tumour-derived cell lines. More complex co-culture models usually rely on sorting procedures for proteome analyses and rarely capture the details of protein glycosylation. Here, we report a strategy termed Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped by transfection with an artificial biosynthetic pathway that transforms bioorthogonally tagged sugars into the corresponding nucleotide-sugars. Only transfected cells incorporate bioorthogonal tags into glycoproteins in the presence of non-transfected cells. We employ BOCTAG as an imaging technique and to annotate cell-specific glycosylation sites in mass spectrometry-glycoproteomics. We demonstrate application in co-culture and mouse models, allowing for profiling of the glycoproteome as an important modulator of cellular function.

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Section: Discussionmentioning

confidence: 99%

Cell-specific bioorthogonal tagging of glycoproteins

et al. 2022

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“…Recently, 1,3-di- O -propionyl-GlcNAl (1,3-Pr 2 GlcNAl) was used to identify O -GlcNAcylated proteins in transgenic mice expressing a mutant of UDP-GlcNAc pyrophosphorylase AGX2 in heart tissue. 162 Anomerically fatty acid-modified GlcNAlk derivatives were presented by the Pratt group as another possibility to prevent nonenzymatic S -glycosylation. 163 The fatty acid ester can be also cleaved inside cells and compensates for the increasing polarity due to the lack of acetyl groups.…”

Section: Application Of Mge: From Cells To Organismsmentioning

confidence: 99%

Metabolic glycoengineering – exploring glycosylation with bioorthogonal chemistry

2023

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“…The deprotected compound is converted to the corresponding GlcNAc‐1‐P analog but requires expression of the F383G mutant of at AGX2 isoform of UAP1 for conversion to the corresponding UDP‐GlcNAc analog. Tissue‐restricted expression of AGX2(F383G) enabled targeted labeling of O‐GlcNAcylated glycoproteins in a living mouse [35] …”

Section: Identifying Protein Substrates Of Glyco‐enzymesmentioning

confidence: 99%

“…Recently, Xing Chen's group used a mutant UAP1 to enable tissue‐specific incorporation of an unnatural GlcNAc analog in a mouse [35] . The Chen lab designed an alkyne‐tagged GlcNAc analog similar to the one used by Cioce et al .…”

Section: Identifying Protein Substrates Of Glyco‐enzymesmentioning

confidence: 99%

Engineering Glyco‐Enzymes for Substrate Identification and Targeting

Burns

Kohler

2022

Israel Journal of Chemistry

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Glycoconjugates are assembled by the coordinate actions of glycosyltransferases, which add sugars, and glycosidases, which remove sugars. These glyco-enzymes comprise families of enzymes that catalyze the same reaction, making it difficult to identify the direct substrates of each isozyme. To solve this challenge, mutagenesis of glycoenzymes has been used to enable incorporation of unnatural sugar analogs that can be employed to tag and isolate the protein substrates of an individual glycosyltransferase. A second challenge arises in efforts to determine which substrates mediate biological effects. Engineering a glycosyltransferase to target its activity toward select acceptor substrates allows deconvolution of the roles of specific glycosylation events. Similarly, glycosidases can be engineered to target specific substrates, with basic science and translational applications. This review describes recent efforts at engineering glyco-enzymes to identify and target their distinct substrates.

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Cell-type-specific labeling and profiling of glycans in living mice

Cited by 32 publications

References 44 publications

Cell-specific bioorthogonal tagging of glycoproteins

Cell-specific bioorthogonal tagging of glycoproteins

Metabolic glycoengineering – exploring glycosylation with bioorthogonal chemistry

Engineering Glyco‐Enzymes for Substrate Identification and Targeting

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