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Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology [Internet]. 3rd edition. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory Press; 2015-2017. doi: 10.1101/glycobiology.3e.009

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Essentials of Glycobiology [Internet]. 3rd edition.

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Chapter 9N-Glycans

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Published online: 2017.

N-Glycans are covalently attached to protein at asparagine (Asn) residues by an N-glycosidic bond. Although diverse sugars are attached to Asn in prokaryotes (Chapters 21 and 22), all eukaryotic N-glycans begin with GlcNAcβ1–Asn and are the focus of this chapter. The biosynthesis of N-glycans is most complex in mammals and is described here in detail. Terminal sugars that largely determine the diversity of N-glycans are described in Chapter 14. Glycosylation-mediated quality control of protein folding by N-glycans is presented in Chapter 39, and the mannose-6-phosphate recognition determinant on N-glycans, necessary for targeting lysosomal hydrolases to lysosomes, is described in Chapter 33. Human congenital disorders of glycosylation arising from defects in N-glycan synthesis are discussed in Chapter 45.


The GlcNAcβ1–Asn linkage was discovered by biochemical analyses of ovalbumin. The minimal amino acid sequence to receive an N-glycan is Asn-X-Ser/Thr in which “X” is any amino acid except Pro. However, not all Asn residues in this sequon are N-glycosylated, as discussed below. Other linkages to Asn include Glc to Asn in laminin of mammals, the S-layer in Archaea and adhesins in some Gram-negative bacteria, GalNAc and GlcNAc to Asn in Archaea, and rhamnose or bacillosamine to Asn in bacteria. In a sweet corn glycoprotein, Arg is found in N-linkage to Glc.

N-Glycan synthesis begins on a lipid-like polyisoprenoid molecule termed dolichol-phosphate (Dol-P) in eukaryotes. Following synthesis of an oligosaccharide that contains as many as 14 sugars, the N-glycan is transferred “en bloc” to protein. This synthetic pathway is conserved in all metazoa, plants, and yeast. Bacteria use related mechanisms to synthesize cell wall (Chapter 21). N-Glycans affect many properties of glycoproteins including their conformation, solubility, antigenicity, activity, and recognition by glycan-binding proteins. Introduction of an N-glycan site (Asn-X-Ser/Thr) is used as a method to localize or orient a glycoprotein or to follow its movement through the cell. Defects in N-glycan synthesis lead to a variety of human diseases (Chapter 45).


All eukaryotic N-glycans share a common core sequence, Manα1-3(Manα1-6)Manβ1-4GlcNAcβ1–4GlcNAcβ1–Asn-X-Ser/Thr, and are classified into three types: (1) oligomannose, in which only Man residues extend the core; (2) complex, in which “antennae” initiated by GlcNAc extend the core; and (3) hybrid, in which Man extends the Manα1-6 arm of the core and one or two GlcNAcs extend the Manα1-3 arm (Figure 9.1).

FIGURE 9.1.. Types of N-glycans.


Types of N-glycans. N-Glycans at Asn-X-Ser/Thr sequons in eukaryote glycoproteins are of three general types: oligomannose, complex, and hybrid. Each N-glycan contains the common core Man3GlcNAc2Asn. Complex N-glycans can have up to six branches initiated (more...)


N-Glycans are added to secreted and membrane-bound glycoproteins at Asn-X-Ser/Thr sequons. About 70% of proteins contain this sequon and ∼70% of sequons carry an N-glycan. Experimental mapping of the murine N-glycoproteome revealed more than 10,000 different N-glycosylation sites. Occasionally, N-glycans occur at Asn-X-Cys and rarely with a different amino acid in the third position. The transfer of an N-glycan to Asn-X-Ser/Thr occurs on the lumenal side of the endoplasmic reticulum (ER) membrane during or after the translocation of the protein substrate. There is no definitive evidence that N-glycans occur on cytoplasmic or nuclear proteins nor on the cytoplasmic portions of membrane proteins. Only Asn-X-Ser/Thr sequons accessible to the ER lumen are known to receive an N-glycan. The identity of “X” may reduce the efficiency of glycosylation, such as when “X” is acidic (Asp or Glu), or enhance the efficiency, such as when Phe is in an adjacent reverse turn. However, although the presence of Asn-X-Ser/Thr is necessary for the receipt of an N-glycan, transfer does not always occur, because of conformational or other constraints during glycoprotein folding. Thus, Asn-X-Ser/Thr sequons encoded by a cDNA are referred to as potential N-glycan sites. Proof that an N-glycan is actually present requires experimental evidence, as described later in this chapter.


N-Glycans of eukaryotes may be released from Asn using the bacterial enzyme peptide-N-glycosidase F (PNGase F). This enzyme will remove oligomannose, hybrid, and complex N-glycans attached to Asn unless the N-glycan core has certain modifications found in slime molds, plants, insects, and parasites. Another enzyme termed PNGase A (from almonds) will remove all N-glycans. Both enzymes are amidases that release N-glycans attached to the nitrogen of Asn, thereby converting Asn to Asp. Therefore, sites of glycosylation can be deduced by amino acid sequence analysis performed before and after PNGase F treatment. Other bacterial enzymes cleave between the two GlcNAc residues of the N-glycan core, leaving one GlcNAc attached to Asn. Endoglycosidase H releases oligomannose and hybrid N-glycans but not complex N-glycans. Endoglycosidase F1 is similar to endoglycosidase H, whereas endoglycosidase F2 releases primarily biantennary N-glycans, and endoglycosidase F3 releases bi- and triantennary N-glycans with a preference for those with a Fuc residue in the core. N-Glycans may also be released by hydrazinolysis or by exhaustive digestion with a protease that removes all amino acids except for the Asn. Released N-glycans may be purified by conventional ion-exchange and size-exclusion chromatography, high-performance liquid chromotography (HPLC) methods, and affinity chromatography on glycan-binding proteins such as lectins. Lectins for glycan analysis are usually obtained from plants (Chapter 48). Release of N-glycans using chemical and enzymic methods, purification, and analysis are described in Chapter 50.


N-Glycan biosynthesis occurs in two phases and in two compartments of eukaryotic cells, the ER and the Golgi (Chapter 4). The first phase is a highly conserved pathway that proceeds at the ER membrane on the lipid carrier Dol-P. An oligosaccharide assembled on Dol-P is transferred to Asn in selected Asn-X-Ser/Thr sequons of secretory and membrane proteins during their translocation into the ER. The second phase begins with processing of N-glycans by glycosidases and glycosyltransferases in the lumen of the ER and continues in the Golgi in a species-, cell type–, protein-, and even site-specific manner. Many of the glycosidases and glycosyltransferases are differentially expressed and exquisitely sensitive to the physiological state of the cell. All glycosyltransferases use activated sugars (nucleotide sugars, dolichol-sugars) as substrates (Chapter 5). Thus, a mature glycoprotein carries N-glycans that depend on the complement of expressed glycosylation genes in the cell type in which the glycoprotein is made and on the physiological state of that cell that may affect the localization and activity of glycosylation enzymes and transporters.

Synthesis of the Dolichol-Linked Precursor

Dolichol is a polyisoprenol lipid comprised of five-carbon isoprene units (Figure 9.2). The most common yeast dolichol has 14 isoprene units, whereas dolichols from other eukaryotes, including mammals, may have up to 19 isoprene units. The structure of the mature N-glycan precursor synthesized on Dol-P is shown in Figure 9.3. Genetic studies in Saccharomyces cerevisiae have identified conserved ALG (Asn-linked glycosylation) loci that encode the biosynthetic machinery for the assembly of the lipid-linked oligosaccharide in eukaryotes (Figure 9.3).

FIGURE 9.2.. Dolichol phosphate (Dol-P).


Dolichol phosphate (Dol-P). N-Glycan synthesis begins with the transfer of GlcNAc-1-P from UDP-GlcNAc to Dol-P to generate dolichol pyrophosphate N-acetylglucosamine (Dol-P-P-GlcNAc). This reaction is inhibited by tunicamycin.

FIGURE 9.3.. Synthesis of Dolichol-P-P-GlcNAc2Man9Glc3.


Synthesis of Dolichol-P-P-GlcNAc2Man9Glc3. Dolichol (red squiggle) phosphate (Dol-P) located on the cytoplasmic face of the endoplasmic reticulum (ER) membrane receives GlcNAc-1-P from UDP-GlcNAc in the cytoplasm to generate Dol-P-P-GlcNAc. Dol-P-P-GlcNAc (more...)

The first step is catalyzed by ALG7 (DPAGT1 in mammals), a GlcNAc-1-phosphotransferase that transfers GlcNAc-1-P from UDP-GlcNAc to form Dol-P-P-GlcNAc. Tunicamycin, an inhibitor of this enzyme, is used to inhibit N-glycosylation in cells. A second GlcNAc and five Man residues are subsequently transferred from UDP-GlcNAc and GDP-Man, respectively, to generate Man5GlcNAc2-P-P-Dol on the cytoplasmic side of the ER membrane (Figure 9.3). All these enzymes transfer only the sugar portion of the nucleotide sugar. The Man5GlcNAc2-P-P-Dol precursor translocates across the ER membrane bilayer via a “flippase” genetically linked to the RFT1 locus in yeast. Man5GlcNAc2-P-P-Dol is extended by the addition of four Man and three Glc residues transferred from Dol-P-Man and Dol-P-Glc, respectively. Dol-P-Man and Dol-P-Glc donors are formed on the cytoplasmic side of the ER membrane from GDP-Man and UDP-Glc. Dol-P-Man and Dol-P-Glc must also be flipped across the ER bilayer. Mammalian MPDU1 is an ER membrane protein necessary for the utilization of Dol-P-Man and Dol-P-Glc in the ER lumen in the synthesis of the mature N-glycan precursor Glc3Man9GlcNAc2-P-P-Dol (Figure 9.3). This 14-sugar glycan is transfered by oligosaccharyltransferase (OST) to Asn in receptive Asn-X-Ser/Thr sequons in protein regions that have translocated across the ER membrane.

Transfer of the Dolichol-Linked Precursor to Nascent Proteins

OST is a multisubunit protein complex in the ER membrane except in the case of the kinetoplastids (Chapter 43). OST catalyzes the transfer of the oligosaccharide from Dol-P-P to Asn-X-Ser/Thr in newly synthesized regions of proteins during passage through the translocon into the ER. OST has a high specificity for the completely assembled oligosaccharide, which is Glc3Man9GlcNAc2 in most eukaryotes. When incomplete oligosaccharides are assembled, transfer efficiency is reduced resulting in hypoglycosylation of glycoproteins that mature with empty N-glycan sites. All OST subunits are transmembrane proteins with between 1 and 13 transmembrane domains. The OST complex cleaves the high-energy GlcNAc-P bond, releasing Dol-P-P in the process (Figure 9.3). Yeast OST is comprised of eight different subunits Stt3p, Ost1p, Wbp1p, Swp1p, Ost2p, Ost4p, Ost5p, and Ost3p or Ost6p. Stt3p is the catalytic subunit of the enzyme. The two OST complexes (containing either of the thioredoxin-subunit Ost3p or Ost6p) have a different protein–substrate specificity. The complexity of OST increases in multicellular organisms. In mammals, there are two different catalytic STT3 subunits that both associate with ribophorins I and II, OST48, OST4, and DAD1 proteins (homologs of the yeast Ost1p, Swp1p, Wbp1p, Ost4p, and Ost2p, respectively). The STT3A complex (OSTA), closely associated with the translocon, contains the KCP2 and DC2 subunits, whereas the STT3B complex (OSTB) that has either MAGT1 or TUSC3 (homologs of Ost3p/Ost6p) glycosylates polypeptides posttranslationally after translocation into the ER. On binding to the catalytic STT3 subunit, the client peptide adopts a 180° turn, making polypeptide folding a competing reaction for N-glycosylation. Indeed, the thioredoxin subunits of the OST complex (Ost3p/Ost6p; MAGT1/TUSC1) modulate the oxidative folding of the client polypeptide thereby extending the polypeptide substrate range of OST. About 600 N-glycosylation sites have been experimentally defined in yeast, and more than 10,000 in murine glycoproteins.

Early Processing Steps: Glc3Man9GlcNAc2Asn to Man5GlcNAc2Asn

Following the covalent attachment of the 14-sugar glycan to Asn-X-Ser/Thr in a protein, processing reactions trim the N-glycan in the ER. The initial steps have key roles in regulating glycoprotein folding via interactions with ER chaperones that recognize specific features of the trimmed N-glycan (Chapter 39). Processing of Glc3Man9GlcNAc2Asn begins with the sequential removal of Glc residues by α-glucosidases I (MOGS) and II (GANAB) (Figure 9.4). Both glucosidases function in the lumen of the ER, with α-glucosidase I acting specifically on the terminal α1–2Glc and α-glucosidase II sequentially removing the two inner α1–3Glc residues. Removal of Glc residues and the transient readdition of the innermost α1–3Glc during protein folding contribute to ER retention time. The removal of Glc may be prevented experimentally by the use of glucosidase I inhibitors such as castanospermine and deoxynojirimycin (Chapter 55). Following inhibition, N-glycans retain the three Glc residues and usually lose one or two Man residues as they pass through the ER and medial-Golgi, resulting in Glc3Man7–9GlcNAc2 structures on mature glycoproteins. Before exiting the ER, ER α-mannosidase I (MAN1B1), removes the terminal α1-2Man from the central arm of Man9GlcNAc2 to yield a Man8GlcNAc2 isomer (Figure 9.4). ER degradation-enhancing α-mannosidase I–like (EDEM) proteins recognize misfolded glycoproteins and target them for ER degradation (Chapter 39). The majority of glycoproteins exiting the ER to the Golgi carry N-glycans with either eight or nine Man residues.

FIGURE 9.4.. Processing and maturation of an N-glycan.


Processing and maturation of an N-glycan. The mature glycan attached to Dolichol-P-P (Figure 9.3) is usually transferred to Asn-X-Ser/Thr sequons during protein synthesis as proteins are being translocated into the endoplasmic reticulum (ER). Some transfer (more...)

Some N-glycans in the cis-Golgi retain a Glc residue because of incomplete processing in the ER. In this case, Golgi endo-α-mannosidase cleaves internally between the two Man residues of the Glcα1-3Manα1-2Manα1-2 moiety, thereby generating a Man8GlcNAc2 isomer different from that produced by ER α-mannosidase I. Trimming of α1-2Man residues continues with the action of α1-2 mannosidases IA and IB (MAN1A1, MAN1A2) in the cis-Golgi to give Man5GlcNAc2 (Figure 9.4), a key intermediate in the pathway to hybrid and complex N-glycans (Figure 9.1). Some Man5GlcNAc2 may also escape further modification. In these cases, a mature membrane or secreted glycoprotein will carry Man5–9GlcNAc2 N-glycans. In addition, the action of ER α-mannosidase I can be blocked experimentally by the inhibitor deoxymannojirimycin, resulting in Man8GlcNAc2 on mature glycoproteins. Most mature glycoproteins have some oligomannose N-glycans that are not processed in the cis-Golgi.

Late Processing Steps: Man5GlcNAc2Asn to Hybrid and Complex N-Glycans

Biosynthesis of hybrid and complex N-glycans (Figure 9.1) is initiated in the medial-Golgi by the action of an N-acetylglucosaminyltransferase called GlcNAc-TI (MGAT1) which adds a GlcNAc residue to the C-2 of the α1-3Man in the core of Man5GlcNAc2 (Figure 9.4). Subsequently, the majority of N-glycans are trimmed by α-mannosidase II enzymes MAN2A1 or MAN2A2 in the medial-Golgi, which remove the terminal α1-3Man and α1-6Man residues from GlcNAcMan5GlcNAc2 to form GlcNAcMan3GlcNAc2. It is important to note that α-mannosidase II cannot trim Man5GlcNAc2 unless it has been acted on by MGAT1. Once both Man residues are removed, a second GlcNAc is added to the C-2 of the α1-6Man in the N-glycan core by the action of GlcNAc-TII (MGAT2) to yield the precursor for all biantennary, complex N-glycans. Hybrid N-glycans are formed if the GlcNAcMan5GlcNAc2 glycan produced by MGAT1 is not acted on by α-mannosidase II. Incomplete action of α-mannosidase II can result in GlcNAcMan4GlcNAc2 hybrids. Small oligomannose N-glycans have been found in relatively large amounts in invertebrates and plants. These Man3–4GlcNAc2 N-glycans (paucimannose N-glycans) are formed from GlcNAcMan3–4GlcNAc2 following removal of the peripheral GlcNAc by a Golgi hexosaminidase that acts after α-mannosidase II (Chapters 24 and 26).

The complex N-glycan shown in the medial-Golgi of Figure 9.4 has two antennae or branches initiated by the addition of two GlcNAc residues. Additional branches can be initiated at C-4 of the core α1-3Man (by GlcNAc-TIV; MGAT4A, MGAT4B) and C-6 of the core α1-6Man by GlcNAc-TV (MGAT5) to yield tri- and tetra-antennary N-glycans (Figure 9.5). MGAT5B or GlcNAc-TIX catalyzes the same reaction but preferentially on O-mannose glycans in brain. Another branch, found in birds and fish, can be initiated at C-4 of the core α1-6Man by GlcNAc-TVI (MGAT6; Figure 9.5). Genes related to GlcNAc-TVI exist in mammalian genomes. Complex and hybrid N-glycans may also carry a “bisecting” GlcNAc residue that is attached to the β-Man of the core by GlcNAc-TIII (MGAT3) (Figure 9.5). A bisecting GlcNAc on a biantennary N-glycan is shown in Figure 9.5, and it may be present in all of the more highly branched N-glycans.

FIGURE 9.5.. Branching and core modification of complex N-glycans.


Branching and core modification of complex N-glycans. The hybrid and mature, biantennary, complex N-glycans shown in Figure 9.4 may contain more branches because of GlcNAc-transferases in the Golgi that act only after MGAT1 has acted. If the α-mannosidase (more...)

Maturation of N-Glycans

Further sugar additions convert the limited repertoire of hybrid and branched N-glycans into an extensive array of mature, complex N-glycans comprising (1) sugar additions to the N-glycan core, (2) elongation of branching GlcNAc residues by sugar additions, and (3) “capping” or “decoration” of elongated branches.

The major core modification in vertebrate N-glycans is the addition of α1-6Fuc to the Asn-linked GlcNAc in the N-glycan core (Figure 9.5). The α1-6fucosyltransferase (FUT8) requires the prior action of MGAT1 (Figure 9.4). In invertebrate glycoproteins, both core GlcNAc residues may receive a Fuc in an α1–3 and/or α1-6 linkage (Chapters 25 and 26). In plants, Fuc is transferred to the Asn-linked GlcNAc only in α1-3 linkage (Chapter 24). Also in plant and helminth glycoproteins, the addition of β1-2Xyl to the β-Man of the core is common. This xylosyltransferase also requires the prior action of MGAT1. Xylose has not been detected in vertebrate N-glycans.

The majority of complex and hybrid N-glycans have extended branches that are made by the addition of Gal to the initiating GlcNAc to produce the ubiquitous building block Galβ1-4GlcNAc, referred to as a type-2 N-acetyllactosamine or“LacNAc”sequence (Figure 9.6). The sequential addition of LacNAc disaccharides gives tandem repeats termed poly-LacNAc. In some glycoproteins, β-linked GalNAc is added to GlcNAc instead of Gal, yielding antennae with a GalNAcβ1–4GlcNAc (LacdiNAc) extension. The structures and biosynthesis of poly-N-acetyllactosamines are discussed further in Chapter 14.

The most important “capping” reactions involve the addition of sialic acids, Fuc, Gal, GlcNAc, and sulfate to complex N-glycan branches. Capping sugars are most commonly α-linked and therefore protrude away from the β-linked poly-LacNAc branches, thus facilitating the presentation of terminal sugars to lectins and antibodies. Many of these structures are shared by N- and O-glycans and by glycolipids (Chapter 14). Terminal Sias can be further modified in various ways (Chapter 15).

The various reactions described above potentially yield a myriad of complex N-glycans that differ in branch number, composition, length, capping arrangements, and core modifications. Some examples to illustrate this diversity are shown in Figure 9.6. Many more examples may be found throughout this book.

FIGURE 9.6.. Typical complex N-glycans found on mature glycoproteins.


Typical complex N-glycans found on mature glycoproteins. A LacNAc unit (bracketed) on any branch may be repeated many times.


Lysosomal hydrolases degrade proteins, lipids, and glycans in the lysosome. Many of these enzymes are targeted to lysosomes by a specialized trafficking pathway that requires phosphorylated oligomannose N-glycans. The phosphorylation step involves the transfer of GlcNAc-1-P to C-6 of Man residues of oligomannose N-glycans on lysosomal hydrolases in the cis-Golgi (Figure 9.4). A glycosidase in the trans-Golgi removes the GlcNAc to generate Man-6-P recognized by Man-6-P receptor (M6PR). M6PRs transport lysosomal hydrolases to an acidified compartment which ultimately fuses with the lysosome. The details of this trafficking pathway are presented in Chapter 33.


The glycosyltransferases in the ER are mainly multitransmembrane proteins woven into the ER membrane. In contrast, the glycosyltransferases in Golgi compartments are generally type II membrane proteins with a small cytoplasmic amino-terminal domain, a single transmembrane domain, and a large lumenal domain that has an elongated stem region extending from the membrane and a globular catalytic domain (Chapter 6). The stem region is often cleaved by signal peptide peptidase-like proteases, particularly SPPL-3, releasing the catalytic domain into the lumen of the Golgi and allowing its secretion. Thus, extracellular soluble forms of many glycosyltransferases exist in tissues and sera. However, extracellular soluble glycosyltransferases are not expected to function as transferases because nucleotide sugars are not known to be present extracellularly. Nucleotide sugars are synthesized in the cytoplasm, except for CMP-sialic acids, which are synthesized in the nucleus (Chapter 5). They are subsequently concentrated in the appropriate compartment following transport across the membrane by specialized nucleotide sugar transporters that translocate CMP-Sias, UDP-Gal, UDP-Glc, UDP-GlcNAc, GDP-Fuc, and other nucleotide sugars. A few of these transporters can transport more than one nucleotide sugar. Each transporter is a multitransmembrane protein that usually contains ten membrane-spanning domains. Some CMP-Sias can be further modified within the lumen of the Golgi by O-acetyl groups before transfer (Chapter 15).


Glycoproteins often have a range of different N-glycans on a particular Asn-X-Ser/Thr N-glycosylation sequon, leading to glycan heterogeneity at each site. Furthermore, when there is more than one Asn-X-Ser/Thr sequon per molecule, different molecules in a population may have different subsets of N-glycans on different sequons, leading to glycoprotein microheterogeneity. Glycoproteins that differ only in their N-glycan complement are termed glycoforms. The variation in N-glycans of a glycoprotein may be due to protein conformation affecting substrate availability for Golgi glycosidases or glycosyltransferases, nucleotide sugar metabolism, transport rate of the glycoprotein through the lumen of the ER and Golgi, and the proximity of an Asn-X-Ser/Thr sequon to a transmembrane domain. Also, localization of glycosyltransferases within subcompartments of the Golgi can determine which enzymes encounter N-glycan acceptors. It is important to note that glycosylation enzymes often compete for the same acceptor and that most glycosyltransferases and glycosidases require the prior actions of other glycosyltransferases and glycosidases before they can act (Figure 9.4).


Determining the functions of N-glycans may be accomplished using inhibitors including tunicamycin that blocks the first step of N-glycosylation, or castanospermine, deoxynojirimycin, and swainsonine that block N-glycan processing; or glycosylation mutants of model organisms such as yeast, cultured mammalian cells, Drosophila melanogaster, Caenorhabditis elegans, zebrafish, and mouse. The various chemical inhibitors of N-glycan synthesis are discussed in Chapter 55. Many yeast mutants in the synthesis and initial processing of N-glycans are identified in Figure 9.3, and three mutants of cultured cells with altered glycosylation are identified in Figure 9.4 and described in detail in Chapter 49. Mutant cells or organisms with an altered N-glycosylation ability provide enormous insights into the biological functions of N-glycans, and their contributions to the biochemical properties of a glycoprotein in terms of structure, activity, susceptibility to proteases, and antigenicity. In addition, mutant cells and organisms allow glycosylation pathways that operate in vivo to be defined. A cell or organism with a loss-of-function mutation usually accumulates the biosynthetic intermediate that is the substrate of the activity lost by the mutant. Gain-of-function mutations reveal alternative pathways or glycosylation reactions that may occur. N-glycan functions have also been determined from the features of human diseases called congenital disorders of glycosylation (CDG) (Chapter 45).

Mouse mutants in particular have provided enormous insights into the functions of individual sugars present in N-glycans, as well as the functions of whole classes of N-glycans. Thus, deletion of the Mgat1 gene that encodes MGAT1 prevents the synthesis of complex and hybrid N-glycans, and Man5GlcNAc2 is found at all complex and hybrid N-glycan sites (Figure 9.4). Whereas the absence of MGAT1 does not affect the viability or growth of Lec1 cultured cells, elimination of MGAT1 in the mouse results in death during embryonic development (Chapter 41). The complex N-glycans are important in retaining growth factor and cytokine receptors at the cell surface, probably through interactions with glycan-binding proteins such as galectins or cytokines, such as transforming growth factor-β. Deletion of genes encoding sialyltransferases, fucosyltransferases, or branching N-acetylglucosaminyltranferases other than MGAT1 has generally produced viable mice with defects in immunity or neuronal cell migration, emphysema, or inflammation. N-Glycans may carry the sugar determinants recognized by selectins that mediate cell–cell interactions important for leukocyte extravasation from the blood stream and regulate lymphocyte homing to lymph nodes (Chapter 34). N-Glycans are known to become more branched when cells become cancerous, and this change facilitates cancer progression (Chapter 47). Tumors formed in mice lacking MGAT5 are retarded in their progression. Thus, certain glycosyltransferases may be appropriate targets for the design of cancer therapeutics.


The authors acknowledge the contribution of Harry Schachter to previous versions of this chapter. The authors appreciate helpful comments and suggestions from Harry Schachter, Yuta Maki, Naoki Nakagawa, Ganesh Subedi, Yasuhiko Kizuka, and Alexandra Walker.


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Copyright 2015-2017 by The Consortium of Glycobiology Editors, La Jolla, California. All rights reserved.

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Bookshelf ID: NBK453020PMID: 28876855DOI: 10.1101/glycobiology.3e.009


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