Golgi Glycosylation

Stanley, Pamela

doi:10.1101/cshperspect.a005199

Cited by 363 publications

(299 citation statements)

References 78 publications

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“…Core glycosylated proteins move to the Golgi via COPII vesicles, and in the Golgi, enzymes sequentially add and modify sugar residues to create the mature glycosylated protein (24). The Sar1 GTPase initiates COPII coat assembly and is required for ER-to-Golgi transport (25,26).…”

Section: Mature (M) Intermediate (I) Deglycosylated (D)mentioning

confidence: 99%

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Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity

Raychaudhuri

Espenshade

2015

Journal of Biological Chemistry

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Section: Mature (M) Intermediate (I) Deglycosylated (D)mentioning

confidence: 99%

“…In fungi, secretory proteins receive mannose-rich core glycosylation in the ER (24). Core glycosylated proteins move to the Golgi via COPII vesicles, and in the Golgi, enzymes sequentially add and modify sugar residues to create the mature glycosylated protein (24).…”

Section: Mature (M) Intermediate (I) Deglycosylated (D)mentioning

confidence: 99%

Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity

Raychaudhuri

Espenshade

2015

Journal of Biological Chemistry

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“…In the second phase of the N-glycosylation pathway, the protein-linked glycan is trimmed by glucosidases and mannosidases (1,9) and is subsequently modified by different glycosyltransferases spatially distributed along the secretory pathway. N-glycan processing enzymes have defined substrate specificities and locations in the secretory pathway (9,10), and their expression level can be regulated upon internal and external signals.…”

mentioning

confidence: 99%

Influence of protein/glycan interaction on site‐specific glycan heterogeneity

Losfeld¹,

Scibona²,

Lin³

et al. 2017

FASEB j.

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To study how the interaction between N-linked glycans and the surrounding amino acids influences oligosaccharide processing, we used protein disulfide isomerase (PDI), a glycoprotein bearing 5 N-glycosylation sites, as a model system and expressed it transiently in a Chinese hamster ovary (CHO)-S cell line. PDI was produced as both secreted Sec-PDI and endoplasmic reticulum-retained glycoprotein (ER)-PDI, to study glycan processing by ER and Golgi resident enzymes. Quantitative site-specific glycosylation profiles were obtained, and flux analysis enabled modeling site-specific glycan processing. By altering the primary sequence of PDI, we changed the glycan/ protein interaction and thus the site-specific glycoprofile because of the improved enzymatic fluxes at enzymatic bottlenecks. Our results highlight the importance of direct interactions between N-glycans and surface-exposed amino acids of glycoproteins on processing in the ER and the Golgi and the possibility of changing a site-specific N-glycan profile by modulating such interactions and thus the associated enzymatic fluxes. Altering the primary protein sequence can therefore be used to glycoengineer recombinant proteins.-Losfeld, M.-E., Scibona, E., Lin, C.-W., Villiger, T. K., Gauss, R., Morbidelli, M., Aebi, M. Influence of protein/glycan interaction on site-specific glycan heterogeneity. FASEB J. 31, 4623-4635 (2017). www.fasebj.org KEY WORDS: glycoengineering • glycobiology • glycoprotein maturation • Golgi processing • enzymatic flux N-glycosylation is a major posttranslational modification of proteins that modulates folding, maturation, trafficking, and secretion, as well as specific protein functions (1-3). Contrary to many other posttranslational modifications, N-glycans are composed of many monosaccharide units, creating a large diversity of glycan structures (4, 5). In eukaryotic cells, the N-glycosylation occurs in the endoplasmic reticulum (ER) after a conserved pathway. The oligosaccharide GlcNAc 2 Man 9 Glc 3 is assembled on the lipid dolicholpyrophosphate at the membrane of the ER and then is covalently linked to the side-chain amide of the asparagine residue in the sequon N-X-S/T by oligosaccharyltransferase (OST) (1, 6, 7). Multiple sites on one glycoprotein can be modified by the OST complex and with the increasing complexity of multicellular organism, an increasing number of N-glycosylation sites in the glycoproteome are observed. It is estimated that up to 6000 different sites are modified by OST in mammalian cells (8). In the second phase of the N-glycosylation pathway, the protein-linked glycan is trimmed by glucosidases and mannosidases (1, 9) and is subsequently modified by different glycosyltransferases spatially distributed along the secretory pathway. N-glycan processing enzymes have defined substrate specificities and locations in the secretory pathway (9, 10), and their expression level can be regulated upon internal and external signals.Glycan maturation in the secretory pathway is not a template-driven process. The...

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“…The appropriate and accurate modification of sugar or glycan to proteins mainly depends on the action of highly specific and precisely located enzymes known as glycosyltransferases and glycosidases in different tissue and cells [22]. It has been reported that activated Ras directs N-glycosylation in transformed cells and that these changes are most readily monitored by the analysis of complextype N-glycosylation.…”

Section: ………………………………………………………………………………mentioning

confidence: 99%

Ras-Directed N-Glycoproteins are Novel Early Biomarkers for Tumorigenesis and Malignant Transformation, and Therapeutic Targets of Neurofibromatosis Type I

Zhu¹

2012

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)MD Anderson cancer center PERFORMING ORGANIZATION REPORT NUMBER1515 Holcombe Blvd Houston,TX77030 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)U.S.Army Medical Research and Material Command Fort Detrick, Maryland 21702 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution unlimited SUPPLEMENTARY NOTES ABSTRACTNeurofibromatosis type I (NF1) is a dominantly inherited disease affecting 3,000 individuals. The hall marker of NF1 is the development of neurofibromas and about 10% of neurofibroma will develop malignant peripheral nerve sheath tumors (MPNSTs). .In this report, we found AXL, c-MET and EGFR are aberrantly expressed in clinical specimens of neurofibromas and MPNSTs, and MPNST cells express high level of glycoproteins. We also found hyperactive Ras unregulated the expression of MGAT5B, one of the glycosyltransferases, to mediate the glycosylation and phosphorylation of kinase receptors in all MPNST cell lines and clinical specimens, and MGT5B shRNA knockdown significantly inhibited the glycosylation and phosphorylation of kinase receptors. We treated cells with 2-Deoxy-D-Glucose (2-DG), a potential glycosylation inhibitor, and found 2-DG inhibited the glycosylation and phosphorylation of AXL, EGFR, and c-MET and impaired receptor-mediated MEK-ERK1/2 and PI3K-AKT signaling in a dose-dependent manner, and inhibited the translocation of receptors from the cytoplasm to the cell surface and retained receptors in the ER and Golgi apparatus, but had no effect on normal human Schwann cells. Furthermore, we found that 2-DG inhibited the tumor development in NF1+/-;p53+/-mice. These novel findings suggest MGAT5B is a novel therapeutic target of NF1 to prevent the tumorigenesis and malignant transformation. SUBJECT TERMS

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Golgi Glycosylation

Cited by 363 publications

References 78 publications

Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity

Endoplasmic Reticulum Exit of Golgi-resident Defective for SREBP Cleavage (Dsc) E3 Ligase Complex Requires Its Activity

Influence of protein/glycan interaction on site‐specific glycan heterogeneity

Ras-Directed N-Glycoproteins are Novel Early Biomarkers for Tumorigenesis and Malignant Transformation, and Therapeutic Targets of Neurofibromatosis Type I

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