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Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000.

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Molecular Cell Biology. 4th edition.

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Section 17.7Protein Glycosylation in the ER and Golgi Complex

As noted previously, most plasma-membrane and secretory proteins contain one or more carbohydrate chains; indeed, the addition and subsequent processing of carbohydrates (glycosylation) is the principal chemical modification to most such proteins. Some glycosylation reactions occur in the lumen of the ER; others, in the lumina of the cis-, medial-, or trans-Golgi cisternae. Thus the presence of certain carbohydrate residues on proteins provide useful markers for following their movement from the ER and through the Golgi cisternae. In this section we first review the structures of the oligosaccharide chains commonly found in glycoproteins and then discuss their synthesis and function.

Different Structures Characterize N- and O-Linked Oligosaccharides

The structures of N- and O-linked oligosaccharides are very different, and different sugar residues are usually found in each type (Figure 17-30). For instance, O-linked oligosaccharides are linked to the hydroxyl group of serine or threonine via N-acetylgalactosamine (GalNac) or (in collagens) to the hydroxyl group of hydroxylysine via galactose. In all N-linked oligosaccharides, N-acetylglucosamine (GlcNAc) is linked to the amide nitrogen of asparagine. O-linked oligosaccharides are generally short, often containing only one to four sugar residues. Typical N-linked oligosaccharides, in contrast, always contain mannose as well as N-acetylglucosamine and usually have several branches each terminating with a negatively charged sialic acid residue. Most cytosolic and nuclear proteins are not glycosylated; the exceptions are several transcription factors and a protein localized to the nuclear- pore complex, which have a single N-acetylglucosamine residue linked to a serine or threonine hydroxyl group.

Figure 17-30. Structures of typical O-linked and N-linked oligosaccharides.

Figure 17-30

Structures of typical O-linked and N-linked oligosaccharides. (a) The O-linked oligosaccharides in glycophorin and many other glycoproteins are linked to the hydroxyl group in serine (Ser) and threonine residues by N-acetylgalactosamine. (more...)

The different structures of N- and O-linked oligosaccharides reflect differences in their biosynthesis. O-linked sugars are added one at a time, and each sugar transfer is catalyzed by a different glycosyltransferase enzyme. In contrast, biosynthesis of N-linked oligosaccharides begins with the addition of a large preformed oligosaccharide, containing 14 sugar residues; subsequently certain sugar residues are removed and others are added, one at a time, in a defined order with each reaction catalyzed by a different enzyme. As described below, the various steps in the formation of both O- and N-linked oligosaccharides occur in specific organelles.

O-Linked Oligosaccharides Are Formed by the Sequential Transfer of Sugars from Nucleotide Precursors

The immediate precursors used in the biosynthesis of oligosaccharides are nucleoside diphosphate or monophosphate sugars (Figure 17-31). The ester bond between the phosphate residue and the carbon atom in the sugar is a high-energy bond with a ΔG°′ of hydrolysis of about −5 kcal/mol. Thus the transfer of the sugar residue to an acceptor hydroxyl group, on a serine or threonine residue or on another sugar residue, is energetically favored.

Figure 17-31. Structures of four sugar nucleotides used in the biosynthesis of oligosaccharides found in glycoproteins.

Figure 17-31

Structures of four sugar nucleotides used in the biosynthesis of oligosaccharides found in glycoproteins. Cleavage of the high-energy phosphoester bond indicated in red provides the energy for transfer of the sugar residue to an acceptor (more...)

All known glycosyltransferases that act on secretory proteins are integral membrane proteins with active sites facing the lumen of the organelle. Each glycosyltransferase is specific for both the donor sugar nucleotide and the acceptor molecule. The galactosyltransferase depicted in Figure 17-32, for instance, only transfers a galactose residue (from UDP-galactose), and only to the 3 carbon atom of an acceptor N-acetylgalactosamine residue. A different enzyme transfers galactose to the 4 carbon of N-acetylglucosamine, and yet another transfers galactose to the 3 carbon of galactose.

Figure 17-32. A specific glycosyltransferase catalyzes addition of a galactose residue from UDP-galactose to carbon atom 3 of N-acetylgalactosamine attached to a protein forming a β1 → 3 linkage.

Figure 17-32

A specific glycosyltransferase catalyzes addition of a galactose residue from UDP-galactose to carbon atom 3 of N-acetylgalactosamine attached to a protein forming a β1 3 linkage. This reaction is the second step in the (more...)

Biosynthesis of the O-linked oligosaccharide in glycophorin and similar glycoproteins (see Figure 17-30a) begins with transfer of N-acetylgalactosamine (GalNAc) from UDP – N-acetylgalactosamine to the hydroxyl group of a serine or threonine residue in the protein. This reaction is catalyzed by a GalNAc transferase that is localized to the rough ER or the cis-Golgi network. After the protein has moved to the trans-Golgi vesicles, a galactose residue is added to the N-acetylgalactosamine by a specific trans-Golgi galactosyltransferase. In vertebrate cells biosynthesis of typical O-linked oligosaccharides is completed by the addition of two negatively charged N-acetylneuraminic acid (also called sialic acid) residues from a CMP precursor (see Figure 17-31); these reactions also occur in the trans-Golgi or the trans-Golgi network.

All the sugar nucleotides used in the synthesis of glycoproteins and glycolipids are made in the cytosol from nucleoside triphosphates and sugar phosphates. Specific antiport proteins in the membranes of the rough ER and Golgi cisternae catalyze the import of the sugar nucleotides into the lumina of these organelles and the export of free nucleotides (UMP, CMP, and GMP) generated within the organelles (Figure 17-33). The one-for-one exchanges catalyzed by these antiporters maintain the concentration of sugar nucleotides in the rough ER and Golgi lumina at a constant level, a requirement for oligosaccharide synthesis.

Figure 17-33. The antiport uptake of nucleotide sugars into Golgi cisternae.

Figure 17-33

The antiport uptake of nucleotide sugars into Golgi cisternae. Both UDP-galactose (UDP-Gal) and UDP – N-acetylgalactosamine (UDP-GalNAc) enter from the cytosol in exchange for UMP; these transport processes are (more...)

ABO Blood Type Is Determined by Two Glycosyltransferases

Image med.jpgThe human A, B, and O blood-group antigens illustrate the importance of specific glycosyltransferases. These antigens, which can trigger harmful immune reactions, are oligosaccharides present on both glycoproteins and glycolipids on the surface of erythrocytes and many other types of cells. Each antigenic determinant consists of one of three structurally related oligosaccharides attached to a ceramide lipid or a serine or threonine residue on a protein (Figure 17-34). The A antigen is similar to O, except that the A antigen contains an N-acetylgalactosamine attached to the outer galactose residue; the B antigen is also similar to O, except for an extra galactose residue attached to the outer galactose.

Figure 17-34. The human ABO blood-group antigens.

Figure 17-34

The human ABO blood-group antigens. The structure of the terminal sugars in the oligosaccharide component of these glycolipids and glycoproteins distinguish the three antigens. The presence or absence of particular glycosyltransferases determine (more...)

All people have the enzymes needed to synthesize the O antigen. People with type A blood also have the GalNAc transferase that adds the extra N-acetylgalactosamine; those with type B blood have the Gal transferase that adds the extra galactose. People with type AB blood have both transferases and synthesize both the A and B antigens; those with type O make only the O antigen. Interestingly, the sequences of GalNAc (A antigen) and Gal (B antigen) transferases differ in just three amino acids, which determine whether the enzyme binds to UDP-Gal or UDP-GalNAc as substrate. Clearly the genes encoding the two enzymes evolved from a common ancestor.

Table 17-5 summarizes the relevance of the A, B, and O antigens to blood transfusions. For example, people who lack the Gal transferase and thus cannot synthesize the B antigen (blood types A and O) normally have antibodies against the B antigen in their serum. Thus, when type B or AB blood is transfused into a person with blood type A or O, the anti-B antibodies of the recipient bind to the transfused erythrocytes and trigger an immune reaction leading to their destruction. To avoid such harmful reactions, blood-group typing and appropriate matching of blood donors and recipients is required in all transfusions.

Table 17-5. ABO Blood Groups.

Table 17-5

ABO Blood Groups.

A Common Preformed N-Linked Oligosaccharide Is Added to Many Proteins in the Rough ER

As noted earlier, biosynthesis of all N-linked oligosaccharides begins in the rough ER with addition of a large preformed oligosaccharide precursor. This precursor oligosaccharide is linked by a pyrophosphoryl residue to dolichol, a long-chain (75 – 95 carbon atoms) polyisoprenoid lipid that is firmly embedded in the ER membrane and acts as a carrier for the oligosaccharide. The dolichol pyrophosphoryl oligosaccharide is formed on the ER membrane in a complex set of reactions catalyzed by enzymes attached to the cytosolic and luminal faces of the rough ER membrane (Figure 17-35). The final dolichol pyrophosphoryl oligosaccharide is oriented so that the oligosaccharide portion faces the ER lumen.

Figure 17-35. Biosynthesis of the dolichol pyrophosphoryl oligosaccharide precursor of N-linked oligosaccharides.

Figure 17-35

Biosynthesis of the dolichol pyrophosphoryl oligosaccharide precursor of N-linked oligosaccharides. Dolichol phosphate (inset) is strongly hydrophobic and long enough to span a phospholipid bilayer membrane four or five times. Two (more...)

The structure of this precursor is the same in plants, animals, and single-celled eukaryotes — a branched oligosaccharide, containing three glucose (Glc), nine mannose (Man), and two N-acetylglucosamine (GlcNAc) molecules, which can be written as Glc3Man9(GlcNAc)2. Five of its 14 residues are conserved in the structures of all N-linked oligosaccharides on secretory and membrane proteins, as can be seen by comparing Figures 17-35 and 17-30b.

The entire Glc3Man9(GlcNAc)2 oligosaccharide is transferred en bloc from the dolichol carrier to an asparagine residue on a nascent polypeptide, a reaction catalyzed by oligosaccharide-protein transferase (Figure 17-36, step 1). Only asparagine residues in the tripeptide sequences Asn-X-Ser and Asn-X-Thr (where X is any amino acid except proline) are substrates for this transferase. Two of the three subunits of the transferase are ribophorins, abundant integral ER membrane proteins whose cytosol-facing domains bind tightly to the larger subunit of the ribosome. This binding localizes the third subunit, which is located within the ER lumen and carries out the transfer reaction, near the growing polypeptide chain. Not all Asn-X-Ser/Thr sequences become glycosylated; for instance, the rapid folding of a segment of a protein containing an Asn-X-Ser/Thr sequence may prevent the transfer of Glc3Man9(GlcNAc)2 to it.

Figure 17-36. Addition and initial processing of N-linked oligosaccharides in the rough ER of vertebrate cells.

Figure 17-36

Addition and initial processing of N-linked oligosaccharides in the rough ER of vertebrate cells. The Glc3Man9(GlcNAc)2 precursor is transferred from the dolichol carrier to a susceptible asparagine residue on a nascent protein as soon (more...)

Immediately after the oligosaccharide is transferred to a nascent polypeptide, all three glucose residues and one particular mannose residue are removed by three different enzymes (Figure 17-36, steps 2 – 4). The three glucose residues, which are the last residues added in synthesis of (Glc)3(Man)9(GlcNAc)2 on the dolichol carrier, appear to act as a signal that the oligosaccharide is complete and ready to be transferred to a protein.

The ER lumen also contains a glucosyltransferase that adds back one glucose residue to a protein-linked Man7 – 9 (GlcNAc)2 oligosaccharide (Figure 17-36, step 3a). This enzyme glucosylates unfolded and misfolded, but not native, folded glycoproteins. The ER also contains two related lectins (carbohydrate-binding proteins) — membrane-attached calnexin and luminal calreticulin — that selectively bind reglucosylated Glc1Man7 – 9(GlcNAc)2 oligosaccharides and prevent folding of the adjacent amino acid segments (see Figure 17-27). Occasionally proteins spontaneously dissociate from calnexin or calreticulin and immediately are deglucosylated; if they then fold properly, they will not be reglucosylated nor rebind to a lectin, and will pass to the Golgi. Thus, like Hsc70, calnexin and calreticulin help prevent premature folding of segments of a newly made protein and also retain unfolded or misfolded proteins within the ER.

Modifications to N-Linked Oligosaccharides Are Completed in the Golgi Complex

Newly made proteins that undergo N-linked glycosylation in the ER enter the Golgi complex bearing one or more Man8(GlcNAc)2 oligosaccharide chains. Biologists traditionally have considered the series of flattened and spherical sacs (cisternae) composing the Golgi complex as a single organelle (Figure 17-37). However, the cis, medial, and trans cisternae of the Golgi contain different sets of enzymes that introduce different modifications to secretory and membrane proteins; thus each region in effect functions as a distinct organelle.

Figure 17-37. Electron micrograph of the Golgi complex in an exocrine pancreatic cell.

Figure 17-37

Electron micrograph of the Golgi complex in an exocrine pancreatic cell. The stacked cisternae of the Golgi complex and a forming secretory vesicle are evident. Elements of the rough ER are on the left in this image. Adjacent to the rough ER are (more...)

Among the enzymes localized to specific regions of the Golgi are those that catalyze additional modifications to the Man8(GlcNAc)2 oligosaccharide chains in glycoproteins produced in the rough ER. Figure 17-38 depicts the sequential reactions that add and remove specific sugar residues to yield a typical N-linked complex oligosaccharide in vertebrate cells. Different enzymes localized to the cis-, medial-, and trans-Golgi cisternae catalyze these reactions as a protein moves through the Golgi complex en route to the cell’s exterior. For instance, galactosyltransferase (reaction 6) is localized to the trans-most Golgi cisternae, and sialyltransferase (reaction 7) is found in the trans-Golgi and the trans-Golgi network. In fact, galactosyltransferase is frequently used as a marker enzyme for trans-Golgi vesicles during subcellular fractionation procedures (see Figures 5-23 and 5-24).

Figure 17-38. Processing of glycoproteins within cis-, medial-, and trans-Golgi cisternae to yield N-linked complex oligosaccharides in vertebrate cells.

Figure 17-38

Processing of glycoproteins within cis-, medial-, and trans-Golgi cisternae to yield N-linked complex oligosaccharides in vertebrate cells. The enzymes catalyzing each step are localized to the indicated compartments. After removal (more...)

Variations in the structures of N-linked oligosaccharides occur as a result of differences in oligosaccharide processing within the ER and Golgi. In some cases, for instance, reactions 1 or 2 in Figure 17-38 may not occur, perhaps because the relevant part of the N-linked oligosaccharide is not accessible to the enzymes catalyzing these reactions. As a consequence, no further carbohydrate modifications will occur since the substrate for the next enzyme in the pathway is not generated. The resulting glycoproteins, which can be secreted, contain a high-mannose oligosaccharide, either Man8(GlcNAc)2 or Man5(GlcNAc)2`, rather than the complex oligosaccharide yielded by the complete pathway shown in Figure 17-38. Other differences in processing yield still other N-linked oligosaccharides in some vertebrate glycoproteins.

Image biotech.jpgProcessing of the common N-linked oligosaccharide precursor, Glc3Man9(GlcNAc)2, often differs among species, posing difficulties for the biotechnology and xenotransplantation industries. For example, most mammals, with the exception of humans and other Old World primates, occasionally add a galactose residue, instead of a N-acetylneuraminic acid residue, to galactose, forming a terminal Gal(α1 → 3)Gal disaccharide on some branches of an N-linked oligosaccharide. Because of persistent infection by microorganisms that contain Gal(α1 → 3)Gal disaccharides, human blood always contains antibodies to this disaccharide epitope. Thus recombinant proteins produced in nonprimate cells frequently are unsuitable for therapeutic use in humans. Moreover, transplantation of organs — such as a heart, pancreas, or liver — from pigs or other animals into humans is thwarted by reaction of human Gal(α1 → 3)Gal antibodies to these epitopes on membrane proteins of the organ, resulting in immediate immune destruction of the transplanted tissue.

Oligosaccharides May Promote Folding and Stability of Glycoproteins

As indicated in Figure 17-35, the antibiotic tunicamycin blocks the first step in formation of the dolichol-linked precursor of N-linked oligosaccharides. Studies with this antibiotic indicate that some proteins require N-linked oligosaccharides in order to fold properly in the ER. In the presence of tunicamycin, for instance, the hemagglutinin precursor polypeptide (HA0) is synthesized, but it cannot fold properly and form a normal trimer (see Figure 17-28); in this case, the protein remains, misfolded, in the rough ER. Moreover, mutation of just one asparagine that normally is glycosylated to a glutamine residue in the HA sequence, thereby preventing addition of an N-linked oligosaccharide to that site, causes the protein to accumulate in the ER in an unfolded state.

Many secretory proteins, however, fold properly and are transported to their final destination even if the addition of all N-linked oligosaccharides is blocked. For example, both glycosylated and nonglycosylated fibronectin (a constituent of the extracellular matrix) are secreted at the same rate and to the same extent by fibroblasts. But nonglycosylated fibronectin, produced in the presence of tunicamycin, is degraded more rapidly by tissue proteases than is normal glycosylated fibronectin. Similarly, recombinant erythropoietin that lacks its normal N-linked oligosaccharides is as potent as the normal hormone in stimulating the growth of erythrocyte precursors in culture. However, when injected into humans, the nonglycosylated hormone is much less potent than the normal protein because it is degraded much faster than normal. These results establish that oligosaccharide chains confer stability on many extracellular glycoproteins.

Oligosaccharides on cell-surface glycoproteins also play a role in cell-cell adhesion (Chapter 22.3). For example, the plasma membrane of white blood cells (leukocytes) contains cell-adhesion molecules (CAMs) that are extensively glycosylated. The oligosaccharides in these molecules interact with a lectin-type domain in certain CAMs found on endothelial cells lining blood vessels. This interaction tethers the leukocytes to the endothelium and assists in their movement into tissues during an inflammatory response to infection.

Mannose 6-Phosphate Residues Target Proteins to Lysosomes

Another function of some N-linked oligosaccharides is to target lysosomal enzymes to lysosomes and prevent their secretion. The addition and initial processing of the preformed N-linked oligosaccharide precursor in the rough ER is the same for lysosomal enzymes as for membrane and secretory proteins (see Figure 17-36). In the cis-Golgi, one or more mannose residues in the resulting Man8(GlcNAc)2 oligosaccharides become phosphorylated via two sequential reactions. In the first reaction, an N-acetylglucosamine phosphate residue is added to the 6-carbon atom of a mannose in the N-linked oligosaccharide by N-acetylglucosamine phosphotransferase, an enzyme specific for lysosomal enzymes (Figure 17-39). The N-acetylglucosamine residue then is removed by a phosphodiesterase in the second reaction, leaving a mannose 6-phosphate (M6P) residue.

Figure 17-39. Phosphorylation of mannose residues on lysosomal enzymes.

Figure 17-39

Phosphorylation of mannose residues on lysosomal enzymes. In the first reaction, an N-acetylglucosamine (GlcNAc) phosphotransferase in the cis-Golgi transfers an N-acetylglucosamine phosphate group to carbon atom 6 of one or more mannose (more...)

Multiple N-linked oligosaccharides are added to most lysosomal enzymes in the rough ER and become phosphorylated in the cis-Golgi. The many M6P residues that are formed then bind to mannose 6-phosphate receptors, which are found primarily in the trans-Golgi network. The luminal domain of this transmembrane protein contains a region that binds M6P very tightly and specifically. As shown in Figure 17-40, vesicles containing the M6P receptor and bound lysosomal enzyme bud from the trans-Golgi network and then fuse with a sorting vesicle, an organelle often termed the late endosome, which has an internal pH of ≈5.5. Because M6P receptors can bind M6P at the slightly acidic pH (≈6.5 – 7) of the trans-Golgi network but not at a pH less than ≈6, the bound lysosomal enzymes are released within late endosomes. Furthermore, a phosphatase within late endosomes generally removes the phosphate from lysosomal enzymes, preventing their rebinding to the M6P receptor.

Figure 17-40. The mannose 6-phosphate (M6P) pathway, the major route for targeting lysosomal enzymes to lysosomes.

Figure 17-40

The mannose 6-phosphate (M6P) pathway, the major route for targeting lysosomal enzymes to lysosomes. Precursors of lysosomal enzymes migrate from the rough ER (left) to the cis-Golgi where mannose residues are phosphorylated. In the (more...)

Two types of vesicles bud from late endosomes. One type contains lysosomal enzymes but not the M6P receptor; after these vesicles bud from late endosomes, they fuse with lysosomes, delivering the lysosomal enzyme to their final destination. The other type of vesicle recycles the M6P receptor back to the trans-Golgi network or, on occasion, to the cell surface.

The lysosomal enzymes we have talked about so far are actually precursors, or proenzymes. These catalytically inactive proenzymes are the ones sorted by the M6P receptor. Late in its maturation a proenzyme undergoes a proteolytic cleavage that causes a conformational change in the protein, forming a smaller but enzymatically active polypeptide. This cleavage occurs in either the acidic late endosome or the lysosome. Delaying the activation of lysosomal proenzymes until they reach the lysosome prevents them from digesting macromolecules in earlier compartments of the secretory pathway.

The M6P sorting pathway for lysosomal enzymes illustrates several important principles that also apply to sorting of secretory and membrane proteins. First, as discussed later, mannose 6-phosphate is one of several sorting signals that target proteins to different compartments within the secretory pathway. Second, membrane-embedded receptors with their bound ligands diffuse into discrete regions of the membrane of an organelle — in this case the trans-Golgi network  — where they are specifically incorporated into budding transport vesicles. Third, these transport vesicles fuse only with one specific organelle, here the late endosome. And finally, cellular transport receptors are recycled after dissociating from their bound ligand.

Lysosomal Storage Diseases Provided Clues to Sorting of Lysosomal Enzymes

Image med.jpgA group of genetic disorders, termed lysosomal storage diseases, are due to the absence of one or more lysosomal enzymes. As a result, undigested glyco-lipids and extracellular components that would normally be degraded by lysosomal enzymes accumulate in lysosomes as large inclusions. I-cell disease is a particularly severe type of lysosomal storage disease in which multiple enzymes are missing from the lysosomes. Cells from affected individuals lack the GlcNAc phosphotransferase that is required for formation of M6P residues on lysosomal enzymes in the cis-Golgi (see Figure 17-39). Biochemical comparison of lysosomal enzymes from normal individuals with those from pa- tients with I-cell disease led to the initial discovery of mannose 6-phosphate as the lysosomal sorting signal. Lacking the M6P sorting signal, the lysosomal enzymes in I-cell patients are secreted rather than sequestered in lysosomes.

When fibroblasts from patients with I-cell disease are grown in a medium containing lysosomal enzymes bearing M6P residues, the diseased cells acquire a nearly normal intracellular content of lysosomal enzymes. This finding indicates that the plasma membrane contains M6P receptors, which can internalize phosphorylated lysosomal enzymes by receptor-mediated endocytosis (see Figure 17-40). This process, used by many cell-surface receptors to bring bound proteins or particles into the cell, is discussed in detail in a later section. It is now known that even in normal cells, some M6P receptors are recycled to the plasma membrane and some phosphorylated lysosomal enzymes are secreted. The secreted enzymes can be retrieved by receptor-mediated endocytosis and directed to lysosomes. This pathway thus scavenges any lysosomal enzymes that escape the usual M6P sorting pathway.

Hepatocytes, the predominant type of liver cells, from patients with I-cell disease contain a normal complement of lysosomal enzymes and no inclusions, even though these cells are defective in mannose phosphorylation. This finding implies that hepatocytes, and perhaps other cell types, employ a M6P-independent pathway for sorting lysosomal enzymes. The nature of this pathway is unknown.

SUMMARY

  • O-linked oligosaccharides, which are bound to serine, threonine, or hydroxylysine residues, are generally short, often containing only one to four sugar residues. All N-linked oligosaccharides, which are bound to asparagine residues, contain a core of three mannose and two N-acetylglucosamine residues and usually have several branches (see Figure 17-30).
  •  Sugar nucleotides synthesized in the cytosol are imported into the rough ER and Golgi cisternae by specific transporters in the membranes of these organelles.
  • O-linked oligosaccharides are formed by the sequential addition of sugars in the ER and Golgi. Addition is catalyzed by various glycosyltransferases that are specific for the donor sugar nucleotide and acceptor molecule (see Figure 17-32).
  •  ABO blood type is determined by whether an individual produces either one or both of two specific glycosyltransferases.
  •  Formation of N-linked oligosaccharides begins with assembly of a ubiquitous 14-residue high-mannose precursor on dolichol, a lipid in the membrane of the rough ER. This preformed oligosaccharide then is transferred to specific asparagine residues of nascent polypeptide chains in the ER lumen.
  •  Enzymes localized in the rough ER and cis-, medial-, and trans-Golgi cisternae remove or add sugar residues to the high-mannose precursor yielding a finished N-linked oligosaccharide (see Figures 17-36 and 17-38). Differences in processing in different proteins, as well as in different cell types and species, produce N-linked oligosaccharides with a variety of structures.
  •   Oligosaccharides attached to glycoproteins may assist in their proper folding, help protect the mature proteins from proteolysis, and in some cases participate in cell-cell adhesion.
  •  Enzymes destined for lysosomes are phosphorylated in the cis-Golgi, yielding multiple mannose 6-phosphate (M6P) residues. M6P receptors in the trans-Golgi network bind the phosphorylated proteins and direct their transfer to late endosomes, where receptors and proteins dissociate. The receptors then are recycled to the Golgi or plasma membrane, and the lysosomal enzymes are delivered to lysosomes (see Figure 17-40). M6P receptors on the cell surface bind extracellular, phosphorylated lysosomal enzymes and, by receptormediated endocytosis, deliver them to lysosomes.

By agreement with the publisher, this book is accessible by the search feature, but cannot be browsed.

Copyright © 2000, W. H. Freeman and Company.
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