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Correspondence to Yanzhuang Wang: Department of Molecular, Cellular and Developmental Biology, University of
Michigan, 830 North University Avenue, Ann Arbor, MI 48109-1048, USA. yzwang@umich.edu
http://dx.doi.org/10.1016/j.jmb.2016.02.030
Edited by T. J. Smith
Abstract
Glycosylation is a ubiquitous modification that occurs on proteins and lipids in all living cells. Consistent with
their high complexity, glycans play crucial biological roles in protein quality control and recognition events.
Asparagine-linked protein N-glycosylation, the most complex glycosylation, initiates in the endoplasmic
reticulum and matures in the Golgi apparatus. This process not only requires an accurate distribution of
processing machineries, such as glycosyltransferases, glycosidases, and nucleotide sugar transporters, but
also needs an efficient and well-organized factory that is responsible for the fidelity and quality control of sugar
chain processing. In addition, accurate glycosylation must occur in coordination with protein trafficking and
sorting. These activities are carried out by the Golgi apparatus, a membrane organelle in the center of the
secretory pathway. To accomplish these tasks, the Golgi has developed into a unique stacked structure of
closely aligned, flattened cisternae in which Golgi enzymes reside; in mammalian cells, dozens of Golgi stacks
are often laterally linked into a ribbon-like structure. Here, we review our current knowledge of how the Golgi
structure is formed and why its formation is required for accurate glycosylation, with the focus on how the Golgi
stacking factors GRASP55 and GRASP65 generate the Golgi structure and how the conserved oligomeric
Golgi complex maintains Golgi enzymes in different Golgi subcompartments by retrograde protein trafficking.
© 2016 Elsevier Ltd. All rights reserved.
0022-2836/© 2016 Elsevier Ltd. All rights reserved. J Mol Biol (2016) 428, 3183–3193
3184 Golgi structure and protein glycosylation
Golgi structure takes part in the most prominent In contrast to the single origination of N-glycosylation,
protein modification, glycosylation. lumenal O-glycosylation is more diverse but the exact
Glycosylation is the most common post-translational mechanism is less well established. There are two
modification of proteins [8–11]. There are two main main forms of O-glycans in higher eukaryotic cells:
forms of protein glycosylation depending on where in shorter mucin-type glycans and longer glycosamino-
the cell proteins are glycosylated. In the cytosol and glycan (GAG) chains on proteoglycans, both of which
nucleus, proteins could be modified with one sugar, are synthesized in the Golgi. Mucin synthesis starts
β-N-acetylglucosamine (GlcNAc), attached to a serine with the attachment of N-acetylgalactosamine to the
or threonine residue. This so-called O-GlcNAcylation side chain of Ser/Thr and is then extended by the
impacts protein–protein interactions and protein stabil- addition of Gal, GlcNAc, sialic acid, and fucose to form
ity and activity, and regulates protein transcription, linear or branched glycans [24]. GAG chains are
metabolism, apoptosis, organelle biogenesis, and attached to Ser through a common core of four sugars
transport [12,13]. In the lumen of the ER and Golgi, (xylose–Gal–Gal–glucuronic acid) in the early Golgi
secretory and transmembrane proteins can be modi- and then extended with repetitive disaccharide units,
fied with oligosaccharides (glycans) attaching to the GlcNAc–glucuronic acid or GlcNAc–iduronic acid, to
side chains of a specific amino acid. Depending on form long linear polymers. The hallmark of GAG
where the sugar chains are attached to a protein, chains is the frequent modification of their sugars with
lumenal glycosylation can be further divided into four sulfate in the trans-Golgi [8]. Rare O-glycans are
groups: (1) N-glycosylation, attached to the amide found to be attached to epidermal growth factor–like
group of asparagine; (2) O-glycosylation, linked to repeats or thrombospondin repeats. These two kinds
the hydroxyl group of serine (Ser), threonine (Thr), of peptide repeats could be modified by O-fucose and
hydroxylysine [14], or tyrosine (Tyr) [15]; (3) C- O-glucose on Ser/Thr and extended in the Golgi
mannosylation, a mannose is attached to the C2 [25–27]. Another less frequent but important O-
atom of tryptophan through a C–C bond [16]; and glycosylation is O-mannosylation. It is initiated with
(4) glypiation, in which a glycan acts as a linker to bridge O-mannose addition in the ER and extended with
a protein to a glycosylphophatidylinositol anchor in the modifications in the Golgi. The best-known O-
membrane [17]. mannose glycan is attached to α-dystroglycan that is
N-glycosylation is the best-characterized form of required for its functional binding to the extracellular
protein glycosylation. Approximately half of human matrix [28,29]. C-mannosylation is unusual since the
proteins are glycoproteins and most of them contain sugar is added to a carbon and it is thought to occur in
N-glycan structures [18]. N-glycans are initially synthe- the ER [30]. Another special form of glycosylation is
sized as a lipid-linked oligosaccharide (LLO) precursor, the formation of glycosylphophatidylinositol anchor
and then the 14-sugar chain GlcNAc2Man9Gluc3 of the that is also named glypiation, initiated in the ER and
LLO is transferred en bloc by the oligosaccharyltrans- matured in the Golgi [31,32].
ferase to the amide group of asparagine of a nascent It is not surprising that diverse protein glycosylation
protein cotranslationally on the lumenal face of the plays critical roles in multiple cellular activities, including
ER [19–21]. Before the proteins are delivered to the protein folding, stability and sorting, protein–protein
Golgi, three glucose and one mannose residues interactions, signal transduction, cell–cell communi-
are removed in the ER. The resulting high-mannose- cations, and immunity [8–11]. Glycosylation defects
type sugar chains, similar to those prevalent in lower have been implicated in a large number of human
eukaryotes, rarely reach the cell surface of more diseases. Congenital disorders of glycosylation
differentiated vertebrate cell types as they are (CDGs) are rare genetic diseases in which both
extensively modified in the Golgi during transport to N-glycan and O-glycan biosyntheses may be defec-
the plasma membrane [22,23]. High-mannose N- tive [33]. Glycosylation defects have also been linked
glycans derived from the ER are further trimmed in the to the pathogenesis of diabetes [34], cancer [35],
cis-Golgi. The addition of GlcNAc on mannose allows and cystic fibrosis [36,37]. For this reason, the fidelity
for generating sugar branches in the medial Golgi. of glycosylation is highly essential. However, as
Decoration of galactose (Gal), sialic acid, and/or opposed to protein and DNA, there is no template
fucose in late Golgi (or trans-Golgi) creates complex for the synthesis of glycan polymers and it has been
N-glycans [11]. A single protein may bear multiple estimated that about 700 proteins are needed to
sugar chains attached to different amino acid resi- generate the diverse glycan structures, including
dues, and sometimes not all sugar chains are glycosyltransferases (addition of sugars), glycosi-
processed equally in the Golgi, resulting in a hybrid dases (removal of sugars), and nucleotide sugar
N-glycan in which some branches keep the high- transporters (supply of sugar substrates) [10]. There-
mannose characteristics, whereas others are deco- fore, protein glycosylation has to be a highly ordered
rated with complex products [11]. Therefore, the and sequential process. As the main sugar chain
diverse glycan structures are created by the elaborate factory, the Golgi apparatus is responsible for utilizing
trimming and processing of the glycan chains in the every element to secure this highly efficient enzymatic
Golgi. event.
Golgi structure and protein glycosylation 3185
GRASPs and the Mechanism of Golgi research revealed proteinaceous connections that
cross-link adjacent cisternae [40–43]; removal of
Structure Formation these proteins by mild proteolysis resulted in Golgi
unstacking [44]. Subsequently, efforts have been
The Golgi is the home to a series of glycosyltrans- made to identify key components in the “Golgi matrix,”
ferases, glycosidases, and nucleotide sugar trans- resulting in the discovery of GRASPs (GRASP55 and
porters that function corporately to complete the GRASP65) and golgins, which work together to
synthesis of various glycans. These enzymes must maintain Golgi structure and function [45].
act on the glycoconjugates in the right place at the right GRASP65 (Golgi reassembly stacking protein of
time. To fulfill this complex task, the Golgi provides 65 kD) was first discovered as a Golgi stacking
specialized membrane-bound compartments for the protein that is accessible to the alkylating reagent
Golgi enzymes to reside and function. The flattening of N-ethylmaleimide only when the Golgi stack is
the cisternae reduces the volume in the lumen, which disassembled [46]. Subsequently, GRASP55 was
may increase the concentration of the enzymes to identified as the homolog of GRASP65 by database
substrates and help maintain a defined microenviron- searching [47]. GRASPs are evolutionally conserved
ment optimized for the enzymes to work (Fig. 1A). In and their orthologs and homologs have been
mammalian cells, dozens of Golgi stacks often laterally identified in different species, including flies [48],
link with each other to form a ribbon-like structure, yeast [49], and parasites [50–52], but not in plants
which is thought to increase the efficiency of Golgi [53]. Both GRASP65 and GRASP55 contain an
function in protein trafficking and glycosylation [38]. N-terminal GRASP domain, which is highly con-
The Golgi structure is not static; rather, it is highly served between the two and across species, and a
dynamic and undergoes rapid disassembly and C-terminal serine/proline-rich domain, which is more
reassembly during mitosis and under stress and divergent. Both GRASPs are peripheral proteins on
physiological conditions [39]. In the last a few decades, the cytoplasmic surface of the Golgi, targeted to
the unique stacked morphology and the dynamic the Golgi membranes via a myristic acid attached to
properties of the Golgi have prompted numerous the N-terminal glycine residue [46]. Cryo-electron
studies focusing on the mechanism of Golgi structure microscopy revealed that GRASP65 is present in
formation and function. Morphological and biochemical cis-Golgi, while GRASP55 is more concentrated in
Fig. 1. The Golgi structure ensures accurate glycosylation. (A) A schematic model showing the significance of Golgi
structure for proper protein glycosylation. GRASP-mediated Golgi cisternal stacking plays three roles: (1) it sets up a
station for the Golgi enzymes to reside and work; (2) it ensures that the cargo molecule travel through the Golgi stack
step-by-step to be sequentially processed by different Golgi glycosylation enzymes; and (3) it restricts vesicle budding and
fusion to the rims of the stack, which slows down trafficking to allow sufficient time for the enzymes to modify the
glycoproteins and enforce accurate glycosylation. COG proteins tethers vesicles that contain Golgi glycosylation enzymes
to Golgi cisternal membranes for fusion, and thus maintain Golgi enzymes in the right subcompartments of the Golgi stack.
The flattening of the Golgi cisternae reduces the lumenal volume within the cisternae, which increases the concentration of
Golgi enzymes to cargo proteins, and helps maintain a microenvironment optimized for the Golgi enzymes. (B) Disruption
of the Golgi structure results in glycosylation defects. Golgi disruption by GRASP depletion increases the accessible areas
for vesicles budding and fusion and accelerates cargo transport through the Golgi membranes, while COG deficiency
results in Golgi enzyme mistargeting and accumulation in vesicles, both of which lead to inaccurate protein glycosylation.
3186 Golgi structure and protein glycosylation
the medial- or trans-cisternae [47]. Both GRASPs [69–71]. The size of GRASP65 trans-oligomers fits
are required for the formation of the polarized well the 11-nm inter-cisternal gap [44]. Together, these
stacked structure (Fig. 1A) [54]. findings show that GRASP55/65 are necessary and
The first evidence for GRASP65 to function as a sufficient for Golgi stack assembly.
stacking factor came from a cell-free assay that mimics In other reports, RNAi-mediated depletion of
Golgi disassembly and reassembly during the cell GRASP65 or GRASP55 also resulted in Golgi ribbon
cycle. Inhibition of GRASP65 using recombinant unlinking, suggesting that GRASPs may link Golgi
proteins or antibodies in the reassembly reaction stacks into a ribbon [38,72]. It is possible that
blocked the formation of Golgi stacks but not the GRASPs function in both Golgi stacking and ribbon
generation of single cisternae [46]. Further biochemical linking by forming trans-oligomers; however, since
studies revealed that GRASP65 forms homodimers the gaps between the stacks are relatively large and
through the GRASP domain; dimers from adjacent heterogeneous (10s to 100s nm), it was speculated
membranes oligomerize in trans and trans-oligomers that other proteins might help GRASPs in ribbon
function as a “glue” to hold the cisternae together into linking. Indeed, a recent study has provided evi-
stacks [55,56]. dence that the actin elongation factor Mena interacts
Oligomerization of the GRASP proteins is regulat- with GRASP65 to promote local actin polymerization
ed by phosphorylation in the cell cycle, which and GRASP65 oligomerization, both of which facilitate
provides an explanation for Golgi disassembly and Golgi ribbon linking [73]. Taken together, these studies
reassembly during cell division [57]. In vitro, treat- provide strong evidence that GRASPs mediate Golgi
ment of Golgi stacks with mitotic kinases that structure formation through trans-oligomerization.
phosphorylate GRASPs led to cisternal unstacking.
In vivo, microinjection of purified mitotic kinases into
interphase cells resulted in Golgi fragmentation. Golgi Structure Formation and Protein
GRASP65 is a major target of mitotic kinases on Glycosylation
the Golgi [55,58], it is phosphorylated by mitotic
kinases cyclin-dependent kinase 1 (Cdk1) and It is generally believed that organelle structure
Polo-like kinase 1 (Plk1), at multiple phosphorylation formation is required for proper functioning. Howev-
sites in the serine/proline-rich domain, which inhibits er, whether or not the formation of Golgi stacks and
GRASP oligomerization and results in mitotic Golgi ribbon is important for different Golgi functions has
disassembly [56]. At the end of mitosis, GRASP65 remained largely a mystery in the field for many
dephosphorylation by PP2A [59] allows the reforma- decades. Golgi cisternae do not normally form
tion of GRASP trans-oligomers and restacking of stacks in the budding yeast (Saccharomyces cere-
newly formed cisternae [60]. GRASP55 is regulated visiae), suggesting that stacking is not absolutely
in a similar way [54], though phosphorylated by the required for cell survival. However, Golgi stacking is
mitogen-activated protein, kinase ERK2 instead a pronounced feature in all metazoans and many
[61–63]. unicellular eukaryotes, implying that it must have
The role of GRASPs in Golgi stack formation has important functional consequences. The best way to
also been assessed in cells. Microinjection of affinity address these questions is to disrupt the Golgi
purified GRASP65 antibodies into mitotic cells stacks and assess the subsequent effects on the
inhibited Golgi stack formation in the daughter cells major functions of the Golgi, including protein
[55,64]. Depletion of GRASP by RNA interference trafficking, glycosylation, and sorting.
(RNAi) reduced the number of cisternae per stack Disruption of the Golgi structure by disrupting
[65], which was rescued by expressing exogenous GRASPs resulted in accelerated protein trafficking. It
GRASP proteins [60]; while simultaneous depletion has been a long thought, without any experimental
of both GRASPs leads to the disassembly of the evidence, that Golgi stack formation increases the
entire stack [54]. efficiency of protein trafficking [74], as the close
Recent structural studies of the GRASP domain also spatial arrangement of cisternae in stacks minimizes
suggested that GRASPs are ideal candidates for the distance that molecules must travel, and local
Golgi stacking. First, in addition to N-myristoylation, tethering proteins facilitate vesicle fusion with Golgi
GRASP65 and GRASP55 also interact with GM130 membranes [75]. However, studies from the
[66] and Golgin-45 [67], respectively. This dual Rothman group and ours have demonstrated that
anchoring of GRASPs onto the Golgi membranes Golgi destruction by the depletion of both GRASPs
restricts the orientation of the protein to favor trans enhanced trafficking of CD8 [76], the vesicular
pairing over cis [68], thus ensuring membrane tethering stomatitis virus G glycoprotein, the cell adhesion
by forming trans-oligomers [55]. Second, the size of the protein integrin, and the lysosomal enzyme cathep-
GRASP proteins fits the tight gap between the sin D [77]. In addition, inhibition of stacking by
cisternae. The crystal structures confirmed that microinjection of GRASP65 antibodies also resulted
the GRASP domain of GRASP55 is globular, with a in accelerated CD8 trafficking [64]. These observa-
6.5-nm diameter, and that this domain forms oligomers tions are contradictory to the original hypothesis that
Golgi structure and protein glycosylation 3187
adhesion and migration, cell–cell communication, and carry Golgi enzymes to the proper subcompartments
immunity [83]. This may explain why stacking is not for function. In the last decade, the conserved
required in yeast, but is essential for many cellular oligomeric Golgi (COG) complex, a membrane tether
activities in higher-order organisms. essential for intra-Golgi trafficking [89–92], has been
An alternative explanation for the glycosylation highlighted for its role in maintaining the Golgi enzymes
defects caused by GRASP depletion is the Golgi to their right locations within the Golgi stack, which
ribbon unlinking. Although the Golgi is a dynamic is critically important for accurate protein glycosylation.
structure, each subcompartment, corresponding to Defects of the COG complex have been linked to
cis-, medial-, and trans-Golgi and the trans-Golgi CDG type II, a growing family of diseases involving
network (TGN), processes specific properties and misregulation of the processing of N- and O-linked
resident components, especially glycosylation en- glycans.
zymes (Fig. 1A) [84,85]. Therefore, the Golgi needs In the secretory pathway, vesicles are tethered to
to develop an effective molecular mechanism to the target membranes to ensure that the vesicles do
maintain its characteristic subcompartments. Consis- not diffuse away. Tethering factors also contribute to
tent with the results that GRASP65 and GRASP55 the specificity and efficiency of membrane fusion.
are differentially localized to cis- and medial- or trans- Together with small Rab GTPases, they dock the
cisternae, acute inactivation of GRASP65 or vesicle to its target compartment, promote
GRASP55 led to a loss of cis- or trans-Golgi integrity, v-SNARE/t-SNARE alignment, and thus facilitate
respectively [86]. Thus, it was proposed that the Golgi membrane fusion. Within the Golgi stack, there are
ribbon formation mediated by the GRASP proteins mainly two types of membrane tethers. One is the
allows Golgi enzymes in the cis, medial, and trans long coiled-coil domain containing golgins that utilize
compartments to synchronize between stacks. When their extended coiled domains for long-range vesicle
one GRASP protein was substituted by the other, the capturing, which is mostly essential for anterograde
Golgi ribbon was intact, but the membranes were de- trafficking [93–95]; the other is a group of proteins
compartmentalized and glycosylation became defec- known as the multisubunit tethering complexes,
tive. Thus, the two GRASPs specifically link analo- including the COGs, which are most likely important
gous cisternae to ensure Golgi compartmentalization, for retrograde trafficking and recycling of Golgi
enzyme localization, and proper glycan processing enzymes.
[86]. Additionally, knockout of GRASP65 in mice also The best-characterized multisubunit tethering
resulted in glycosylation defects at the cell surface complexes in the Golgi is the COG complex, a
[87]. In summary, GRASP proteins function as the hetero-oligomer consisting of eight subunits, COG1–
glue that holds and stacks together the Golgi cisterna COG8, which display as two lobes, COG1–COG4 in
to form the Golgi structure, which controls the cargo lobe A, and COG5–COG8 in lobe B; these two lobes
flux through the Golgi stack, and thus ensures are interconnected by a COG1–COG8 interaction
accurate protein glycosylation (Fig. 1A). [96–102]. COGs are peripheral membrane proteins
GRASP depletion also caused missorting of that exist in cells either in soluble or membrane-
cathepsin D precursor to the extracellular space bound forms. Membrane-bound COGs are present
[77]. So far, it is unclear whether the missorting is in different arrangements [103], including the
caused by defects in protein glycosylation (and thus complete COG1–8 complex, lobe A and lobe B
defects in mannose-6 phosphorylation, a signal for subcomplexes. The COG complex interacts with
lysosomal sorting), or by dysfunction of the sorting all classes of molecular machinery maintaining intra-
machinery in the TGN. In polarized cells such as Golgi trafficking, including SNAREs, SNARE-
neurons and epithelial cells, N- and O-linked interacting proteins, Rabs, coiled-coil tethers, vesic-
glycosylation serve as apical sorting signals [88]. ular coats, and molecular motors. It is also proposed
These results indicate that stacking may ensure that to play three possible roles: direct function in vesicle
sorting occurs only when cargo molecules are tethering [98,104,105], assembly of vesicle docking
properly glycosylated and have reached the TGN, stations [92,106], and stabilization of SNARE com-
but not in earlier subcompartments. plexes [106–109]. The characteristics and functions
of the COG complex have been well summarized by
Willett and colleagues [110].
Golgi Trafficking Machinery and Protein Most importantly, the COG complex plays essen-
Glycosylation tial roles in targeting and recycling of Golgi glyco-
sylation enzymes (Fig. 1A). Most of the CDGs have
As the Golgi is a dynamic structure, Golgi enzymes been linked to defective enzymes or transporters.
must stay in the right place where they perform their However, around one-third of the remaining patients
functions while substrate molecules constantly flow have mutations in the subunits of the COG complex
through the membrane stacks (Fig. 1A). In addition to [90]. So far mutations in seven out of the eight COG
the flattened cisternae, each Golgi stack is surrounded subunits (except COG3) have been identified in
by multiple transport vesicles, which are thought to clinical phenotypes and glycosylation abnormalities
Golgi structure and protein glycosylation 3189
[33]. Several COG subunits are either severely leads to dramatic and broad glycosylation defects,
truncated or rapidly degraded in some CDG type II but so far, no GRASP mutants have been identified in
diseases [33]. Loss of one COG subunit also CDG patients. One possibility is that GRASP func-
destabilizes the other subunits and reduces their tions and Golgi structure formation may be critically
expression, and a series of studies on COG-deficient important for cellular functions, and thus, deletion of
CDG patients showed that the glycosylation defi- GRASPs may be lethal. Another more likely possibility
ciencies are widespread, extending from very early is that GRASPs may be post-translationally modified
demannosylation defects to late sialylation defects rather than mutated and degraded in diseases, which
[111]. so far has not been studied. For instance, GRASPs
Studies on COG3 and COG7 in HeLa cells phosphorylation occurs not only in mitosis as a way to
indicated that the depletion of these components regulate Golgi disassembly and reassembly during
caused extensive Golgi fragmentation and led to an the cell cycle, but also in abnormal pathological
accumulation of COG-dependent vesicles carrying conditions [78] and upon stimulation with growth
Golgi enzymes MAN2A1 and GALNT2 (Fig. 1B) factors for cell migration [116]. Therefore, future
[104,112], indicating that in COG-deficient cells, a studies should determine whether GRASPs are
significant fraction of Golgi glycosylation enzymes phosphorylated or downregulated in human diseases
are separated from the target proteins that travel where Golgi fragmentation and protein glycosylation
through the Golgi stack. COG mutations impair defects have been observed. In addition, whether
retrograde but not anterograde trafficking of Golgi Golgi structural defects affect other type of glycosyl-
enzymes [113–115]. Therefore, COG-mediated ation in addition to the N-type remains unexploited.
retrograde trafficking is crucial for maintaining the Thus, further investigation of GRASPs and COGs in
accurate localization of glycosylation enzymes in the relation to Golgi structure formation and function may
Golgi stack. These results further suggest that Golgi provide meaningful insights into disease therapy.
structure formation and function in trafficking and
glycosylation are tightly coupled.
Acknowledgments
Conclusion and Perspectives We thank Toshihiko Katoh, Kazuhiro Aoki, and
Michael Tiemeyer for their glycomic studies of
The Golgi is an essential subcellular organelle with GRASP-depleted cells, members in the Wang lab
a complex stacked structure and delicate functions for insightful discussions, and Courtney Killeen for
in protein trafficking, sorting, and glycosylation; the proofreading the manuscript. This work was support-
structural–functional relationship of this membrane ed in part by the National Institutes of Health (Grants
organelle is particularly intriguing. Recent studies GM087364, GM105920, and GM112786), the
on the GRASP proteins provided a possibility to American Cancer Society (Grant RGS-09-278-01-
understand the molecular mechanism of Golgi CSM), MCubed, and the Fastforward Protein Folding
structure formation and also provided a tool to Disease Initiative of the University of Michigan, and an
disrupt the Golgi structure and thereby dissect the anonymous donation to Y.W.
biological significance of Golgi structure formation in Conflict of Interest Statement: The authors
relation to Golgi functions such as glycosylation. declare no conflicts of interest.
Although GRASP depletion resulted in glycosylation
defects, no evidence has been provided for an Received 31 December 2015;
interaction between GRASPs and Golgi enzymes. Received in revised form 27 February 2016;
Thus, it is unlikely that GRASPs play direct roles in Accepted 28 February 2016
protein glycosylation. In contrast to GRASPs, the Available online 5 March 2016
COG complex plays a direct role in targeting and
recycling Golgi enzymes into the different subcom- Keywords:
partments within the Golgi stack. It is possible that protein glycosylation;
GRASPs set up the infrastructure of the Golgi stacks Golgi stacks;
for the glycosylation enzymes to reside and work, GRASPs;
COGs locate the enzymes to specific subcompart- COG complex;
ments, and other Golgi structural proteins, such as CDG
golgins, control the transport of substrate molecules
through the Golgi stack (Fig. 1A), although the Abbreviations used:
precise mechanism that coordinates these machin- CDG, congenital disorders of glycosylation; COG, con-
eries to ensure accurate glycosylation needs to be served oligomeric Golgi; ER, endoplasmic
elucidated. reticulum; GAG, glycosaminoglycan; GlcNAc, β-N-
Many questions regarding the Golgi structure and acetylglucosamine; LLO, lipid-linked oligosaccharide; RNAi,
function still remain. For example, GRASP depletion RNA interference; TGN, trans-Golgi network.
3190 Golgi structure and protein glycosylation
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