The biosynthesis of highly branched N-glycans: studies on the sequential pathway and functional role of N-actylglucosaminyltransferases I, II, III, IV, V and VI

Brockhausen, Inka; Narasimhan, Saroja; Schachter, Harry

doi:10.1016/0300-9084(88)90289-1

Cited by 87 publications

(55 citation statements)

References 44 publications

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“…The molecular mechanisms underlying the N-glycan regulation of the invasive function of MMP9 in placenta need to be elucidated. Here, we found that MGAT5 specific RNA interference in the explants and MGAT5 is, an important glycosyltransferase involved in the formation of branching asparagine-linked oligosaccharides [38]. Integrins contain nearly 20-30 consensus N-glycosylation sites in both α-and β -subunits, modifications of these N-glycans on integrins have the potential to alter cell function and behavior [39].…”

Section: Discussionmentioning

confidence: 97%

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

et al. 2015

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Section: Discussionmentioning

confidence: 97%

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

et al. 2015

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“…An increase in ␤1,6-GlcNAc branching of N-glycans as a consequence of enhanced expression of N-acetylglucosaminyltransferase V (GnT-V) 2 is convincingly correlated with the increased frequency of tumor metastasis (3-6). N-Acetylglucosaminyltransferase III (GnT-III) is one more important glycosyltransferase that has been receiving much attention for its involvement in the biology of tumor (7,8). It catalyzes the transfer of N-acetylglucosamine (GlcNAc) in a ␤1,4 linkage to mannose on N-glycans forming a bisecting GlcNAc structure.…”

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confidence: 99%

Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels

Isaji

et al. 2016

Journal of Biological Chemistry

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N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits ␣2,3-sialylation but not ␣2,6-sialylation. The migratory ability of cells without or with a low level of ␣2,6-sialylation is consistently suppressed after GnT-III overexpression. In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly ␣2,6-sialylated. Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. Interestingly, up-regulation of ␣2,6-sialylation by overexpressing ␤-galactoside ␣2,6-sialyltranferase 1 in the ␣2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. Conversely, depletion of ␣2,6-sialylation by knock-out of ␤-galactoside ␣2,6-sialyltranferase 1 in ␣2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. Taken together, our data clearly demonstrate that high expression of ␣2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis.Alterations in N-linked glycosylation have been observed in various malignant diseases such as cancer. Certain glycan structures resulting from the dysregulated glycosyltransferases and glycosidases are well known tumor markers and closely associated with the malignant progression (1). As examples, the ␣1,6-fucosylated ␣-fetoprotein catalyzed by ␣1,6-fucosyltransferase has been developed as a biomarker for primary hepatoma by Abelev (2). An increase in ␤1,6-GlcNAc branching of N-glycans as a consequence of enhanced expression of N-acetylglucosaminyltransferase V (GnT-V) 2 is convincingly correlated with the increased frequency of tumor metastasis (3-6). N-Acetylglucosaminyltransferase III (GnT-III) is one more important glycosyltransferase that has been receiving much attention for its involvement in the biology of tumor (7,8). It catalyzes the transfer of N-acetylglucosamine (GlcNAc) in a ␤1,4 linkage to mannose on N-glycans forming a bisecting GlcNAc structure. This step plays critical roles in determining the structure of N-glycans because introduction of the bisecting GlcNAc residue could preclude further processing and elongation of N-glycans, such as the formation of ␤1,6-GlcNAc branching structures (9). Considering also that overexpression of GnT-III inhibited the metastasis of multiple types of carcinomas (10, 1...

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“…N-acetylglucosaminyltransferases (GlcNAcTs, GnTs) (as productions of Mgat genes) conduct the production of Tri and tetraantennary and more branched, complex N-glycans in Golgi apparatus. Sequential activity rules for the GnTs were established by Brockhausen Karacali S. Cell Surface Sialylated N-Glycan Alterations et al (89). These enzymes are responsible for the branching of the core structure in vitro (90)(91)(92)(93)(94).…”

Section: Differentiated Cell Sialylated N-glycansmentioning

confidence: 99%

Cell Surface Sialylated N-Glycan Alterations during Development

Karaçalı¹

2017

Eur J Biol

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This brief survey focuses on the comparison of sialylated N-glycans of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and of differentiated cells. In addition, the impact of sialic acid (Sia) deficiency on cell surfaces during development is summarized. The most common Sia is N-acetylneuraminic acid (Neu5Ac). The branched structures of complex-and hybrid-type N-glycans are the carrier for Sia. Transmembrane adhesive proteins, voltage-gated ion channels and many ligand-activated receptors are some examples of heavily sialylated N-glycan bearing membrane proteins. Their oligosaccharide extensions provide an important contribution to glycocalyx glycans. ESCs and iPSCs are characterized with high mannose-type and biantennary complex-type core structures. Two branches terminate with α2,6-linked Sia. MSCs contain high mannose, hybrid-and complex-type N-glycans. Linear poly-N-acetyllactosamine (poly-Galβ1-4GlcNAc, poly-LacNAc) chains are the characteristic structures. Both α2,3-and α2,6-linked Sias are seen in a species-specific manner in MSCs. α2,6-linked Sia is probably a marker associated with the multipotency of human MSCs. Differentiated healthy cells contain the most abundant 2-branched complex structures. The bisecting branch on the core structure appears as a differentiation marker. poly-LacNAc chains are terminated with α2,3-and α2,6-linked Sia, with the former being higher. poly-LacNAc sequences have a high affinity for β-galactoside recognizing lectin and galectin. Galectin forms a lattice structure with the N-glycans of glycoproteins anchored to the plasma membrane. The impact of N-glycangalectin complexes in cell biology is summarized. Finally, the effect of reduced Sia on clearance of aged cells is explained. Experimental evidence for the masking role of Sia in the regulation of histolysis in aged cells is revealed.

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The biosynthesis of highly branched N-glycans: studies on the sequential pathway and functional role of N-actylglucosaminyltransferases I, II, III, IV, V and VI

Cited by 87 publications

References 44 publications

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

N-acetylglucosaminyltransferase V inhibits the invasion of trophoblast cells by attenuating MMP2/9 activity in early human pregnancy

Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels

Cell Surface Sialylated N-Glycan Alterations during Development

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