Novel glycosylation routes for glycoproteins: the lacdiNAc pathway

Eijnden, D. H. Van Den; Neeleman, Alex P.; Knaap, W.P.W. van der; Bakker, Hans; Agterberg, Marja; Die, Irma van

doi:10.1042/bst0230175

Cited by 59 publications

(35 citation statements)

References 16 publications

(17 reference statements)

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“…lactoferrin, but is in general more commonly found in the insect glycome (Van den Eijnden et al, 1995). So far, activity towards LacdiNAc and/or LacNAc structures in specific glycoproteins or glycolipids has not been demonstrated.…”

Section: Substrate Specificities Of Catalytic Domains Relevant To Virmentioning

confidence: 99%

Bacterial chitinases and chitin-binding proteins as virulence factors

et al. 2013

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Section: Substrate Specificities Of Catalytic Domains Relevant To Virmentioning

confidence: 99%

Bacterial chitinases and chitin-binding proteins as virulence factors

et al. 2013

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“…LN, which can be found in both vertebrate and invertebrate glycoproteins (49). Among the vertebrates, LDN is a common terminal disaccharide of pituitary hormone N-glycans, in which the N-acetylgalactosamine residues are 4-O-sulfated and function as recognition markers for hormonal clearance (93,94).…”

Section: Cloning and Functional Analysis Of Tn␤4galnact 33515mentioning

confidence: 99%

“…The results unequivocally confirmed that the new cDNA isolated in this study encodes a ␤4-N-acetylgalactosaminyltransferase involved in Nglycoprotein glycan elongation. Thus, this cDNA encodes the enzyme involved in the synthesis of GalNAc-␤4GlcNAc-R, also known as LacDiNAc or LDN, which is found in the terminal regions of some N-glycans (49,50), including those of some T. ni glycoproteins (43). This gene product can account for the ␤4-N-acetylgalactosaminyltransferase activity originally detected in T. ni cells by van Die et al (30).…”

mentioning

confidence: 98%

Molecular Cloning and Functional Characterization of a Lepidopteran Insect β4-N-Acetylgalactosaminyltransferase with Broad Substrate Specificity, a Functional Role in Glycoprotein Biosynthesis, and a Potential Functional Role in Glycolipid Biosynthesis

Vadaie

Jarvis

2004

Journal of Biological Chemistry

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A degenerate PCR approach was used to isolate a lepidopteran insect cDNA encoding a ␤4-galactosyltransferase family member. The isolation and initial identification of this cDNA was based on bioinformatics, but its identification as a ␤4-galactosyltransferase family member was experimentally confirmed. The newly identified ␤4-galactosyltransferase family member had unusually broad donor and acceptor substrate specificities in vitro, as transfered galactose, N-acetylglucosamine, and N-acetylgalactosamine to carbohydrate, glycoprotein, and glycolipid acceptors. However, the enzyme preferentially utilized N-acetylgalactosamine as the donor for all three acceptors, and its derived amino acid sequence was closely related to a known N-acetylgalactosaminyltransferase. These data suggested that the newly isolated cDNA encodes a ␤4-N-acetylgalactosaminyltransferase that functions in insect cell glycoprotein biosynthesis, glycolipid biosynthesis, or both. The remainder of this study focused on the role of this enzyme in N-glycoprotein biosynthesis. The results showed that the purified enzyme transferred N-acetylgalactosamine, but no detectable galactose or N-acetylglucosamine, to a synthetic N-glycan in vitro. The structure of the reaction product was confirmed by chromatographic, mass spectroscopic, and nuclear magnetic resonance analyses. Co-expression of the new cDNA product in insect cells with an N-glycoprotein reporter showed that it transferred N-acetylgalactosamine, but no detectable galactose or N-acetylglucosamine, to this N-glycoprotein in vivo. Confocal microscopy showed that a GFP-tagged version of the enzyme was localized in the insect cell Golgi apparatus. In summary, this study demonstrated that lepidopteran insect cells encode and express a ␤4-N-acetylgalactosaminyltransferase that functions in N-glycoprotein biosynthesis and perhaps in glycolipid biosynthesis, as well. The isolation and characterization of this gene and its product contribute to our basic understanding of insect protein N-glycosylation pathways and to the growing body of evidence that insects can produce glycoproteins with complex N-glycans.

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“…One of the glycan sequences of interest is the LacdiNAc (GalNAcb1-4GlcNAc) motif, which is synthesized by b4GalNAc-T3 [35]. LacdiNAc is frequently present on glycoproteins and glycolipids in invertebrates but is only present on a limited number of glycoproteins and glycolipids, such as glycoprotein hormones, in vertebrates [36,37]. At present, the roles of LacdiNAc in mammalian cells are not fully understood.…”

Section: Introductionmentioning

confidence: 99%

LacdiNAc (GalNAcβ1-4GlcNAc) Contributes to Self-Renewal of Mouse Embryonic Stem Cells by Regulating Leukemia Inhibitory Factor/STAT3 Signaling

et al. 2011

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Self-renewal of mouse embryonic stem cells (mESCs) is maintained by leukemia inhibitory factor (LIF)/signal transducer and activator of transcription (STAT3) signaling. However, this signaling control does not function in neither mouse epiblast stem cells (mEpiSCs) nor human ESCs (hESCs) or human induced pluripotent stem cells (hiPSCs). To date, the underlying molecular mechanisms that determine this differential LIF-responsiveness have not been clarified. Here, we show that the cell surface glycan LacdiNAc (GalNAcb1-4GlcNAc) is required for LIF/ STAT3 signaling. Undifferentiated state mESCs expressed LacdiNAc at a higher level than differentiated state cells. Knockdown of b4GalNAc-T3 reduced LacdiNAc expression and caused a decrease in LIF/STAT3 signaling that lessened the rate of self-renewal of mESCs. A biochemical analysis showed that LacdiNAc expression on LIF receptor (LIFR) and gp130 was required for the stable localization of the receptors with lipid raft/caveolar components, such as caveolin-1. This localization is required for transduction of a sufficiently strong LIF/STAT3 signal. In primed state pluripotent stem cells, such as hiPSCs and mEpiSC-like cells produced from mESCs, LacdiNAc expression on LIFR and gp130 was extremely weak and the level of localization of these receptors on rafts/caveolae was also low. Furthermore, knockdown of b4GalNAc-T3 decreased LacdiNAc expression and reduced the efficiency of reversion of primed state mEpiSC-like cells into naïve state mESCs. These findings show that the different LIF-responsiveness of naïve state (mESCs) and primed state (mEpiSCs, hESCs, and hiPSCs) cells is dependent on the expression of LacdiNAc on LIFR and gp130 and that this expression is required for the induction and maintenance of the naïve state. STEM CELLS 2011;29:641-650 Disclosure of potential conflicts of interest is found at the end of this article.

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Novel glycosylation routes for glycoproteins: the lacdiNAc pathway

Cited by 59 publications

References 16 publications

Bacterial chitinases and chitin-binding proteins as virulence factors

Bacterial chitinases and chitin-binding proteins as virulence factors

Molecular Cloning and Functional Characterization of a Lepidopteran Insect β4-N-Acetylgalactosaminyltransferase with Broad Substrate Specificity, a Functional Role in Glycoprotein Biosynthesis, and a Potential Functional Role in Glycolipid Biosynthesis

LacdiNAc (GalNAcβ1-4GlcNAc) Contributes to Self-Renewal of Mouse Embryonic Stem Cells by Regulating Leukemia Inhibitory Factor/STAT3 Signaling

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