Abstract:
:Glycoproteins perform extra- and intracellular functions in innate and adaptive immunity by lectin-based interactions to exposed glyco-determinants. Herein, we document and mechanistically explain the formation of subcellular-specific N-glycosylation determinants on glycoproteins trafficking through the shared biosynthetic machinery of human cells. LC-MS/MS-based quantitative glycomics showed that the secreted glycoproteins of eight human breast epithelial cells displaying diverse geno- and phenotypes consistently displayed more processed, primarily complex type, N-glycans than the high-mannose-rich microsomal glycoproteins. Detailed subcellular glycome profiling of proteins derived from three breast cell lines (MCF7/MDA468/MCF10A) demonstrated that secreted glycoproteins displayed significantly more α-sialylation and α1,6-fucosylation, but less α-mannosylation, than both the intermediately glycan-processed cell-surface glycoproteomes and the under-processed microsomal glycoproteomes. Subcellular proteomics and gene ontology revealed substantial presence of endoplasmic reticulum resident glycoproteins in the microsomes and confirmed significant enrichment of secreted and cell-surface glycoproteins in the respective subcellular fractions. The solvent accessibility of the glycosylation sites on maturely folded proteins of the 100 most abundant putative N-glycoproteins observed uniquely in the three subcellular glycoproteomes correlated with the glycan type processing thereby mechanistically explaining the formation of subcellular-specific N-glycosylation. In conclusion, human cells have developed mechanisms to simultaneously and reproducibly generate subcellular-specific N-glycosylation using a shared biosynthetic machinery. This aspect of protein-specific glycosylation is important for structural and functional glycobiology and discussed here in the context of the spatio-temporal interaction of glyco-determinants with lectins central to infection and immunity.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Lee LY,Lin CH,Fanayan S,Packer NH,Thaysen-Andersen Mdoi
10.3389/fimmu.2014.00404subject
Has Abstractpub_date
2014-08-25 00:00:00pages
404issn
1664-3224journal_volume
5pub_type
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02581
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00133
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01186
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00487
更新日期:2017-04-25 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01496
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02533
更新日期:2018-10-30 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.01757
更新日期:2017-12-12 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02877
更新日期:2018-12-11 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.01240
更新日期:2020-06-23 00:00:00
abstract::[This corrects the article DOI: 10.3389/fimmu.2019.00917.]. ...
journal_title:Frontiers in immunology
pub_type: 已发布勘误
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journal_title:Frontiers in immunology
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pub_type: 已发布勘误
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2020.00746
更新日期:2020-05-05 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2017.00731
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doi:10.3389/fimmu.2019.03154
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.3389/fimmu.2020.593748
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