Golgi apparatus

The Golgi apparatus is named after the Italian physician and scientist Camillo Golgi, who discovered the fine membranous structure of the organelle in 1898. In mammalian cells, the Golgi apparatus has a morphologically distinct architecture. It consists of stacks of interconnected membrane cisternae, and resides close to the nucleus in proximity to the microtubule organizing center. It plays a central role in the intracellular transport of newly synthesized proteins and membrane lipids to other organelles, as well as in the transport of substances that are secreted to the extracellular space. Proteins present in the Golgi apparatus take part in various steps in this trafficking process, being involved in the post-translational modification, packaging and sorting of proteins.

In the subcellular resource, 1256 genes (6% of all protein-coding human genes) have been shown to encode proteins that localize to the Golgi apparatus (Figure 2). A Gene Ontology (GO)-based functional enrichment analysis of genes encoding proteins that localize to the Golgi apparatus mostly shows enrichment of terms related to regulation of cell size, transmembrane- and vesicle transport, as well as protein metabolism and processing. Around 79% (n=986) of the Golgi apparatus proteins localize to one or more additional cellular compartments, the most common ones being the nucleus and vesicles. Examples of Golgi-associated proteins can be found in Figure 1.


GORASP1 - HeLa

GORASP2 - A-431

SLC30A6 - A-431

Figure 1. Examples of proteins localized to the Golgi apparatus. GORASP1 is a key protein for maintaining the structure of the Golgi apparatus, especially for the reassembly of the fragmented Golgi apparatus after its breakdown during mitosis (detected in HeLa cells). GORASP2 has a similar function to GORASP1 and is also involved in the assembly and stacking of Golgi-cisternae (detected in A-431 cells). SLC30A6 is a Golgi membrane protein that regulates the zinc ion transport between the Golgi lumen and the cytosol (detected in A-431 cells).

0%10%20%30%40%50%60%70%80%90%100%% genesNot mappedSecretedOther organellesGolgi apparatus

  • 6% (1256 proteins) of all human proteins have been experimentally detected in the golgi apparatus by the Human Protein Atlas.
  • 277 proteins in the golgi apparatus are supported by experimental evidence and out of these 63 proteins are enhanced by the Human Protein Atlas.
  • 986 proteins in the golgi apparatus have multiple locations.
  • 173 proteins in the golgi apparatus show single cell variation.

  • Proteins localizing to the Golgi apparatus are mainly involved in regulation of cell size, cellular, transport and modification of proteins.

Figure 2. 6% of all human protein-coding genes encode proteins localized to the Golgi apparatus. Each bar is clickable and gives a search result of proteins that belong to the selected category.

The structure of the Golgi apparatus

In human cells, the Golgi apparatus is made up of a series of flattened membrane-bound disks, known as cisternae, originating from fusion of vesicular clusters that bud off the endoplasmatic reticulum (ER) (Kulkarni-Gosavi P et al. (2019); Short B et al. (2000)). The membrane disks are arranged in consecutive compartments that are named after the direction in which proteins move through them. Proteins coming from the ER or from the ER-Golgi intermediate compartment (ERGIC) enter in the cis Golgi network (CGN), followed by the medial-Golgi compartment, and ultimately exit via the adjacent trans Golgi Network (TGN) on route to their final destinations. The Golgi-membranes are characterized by constant emergence and fusion of small transport vesicles trafficking between the compartments. In most human cells, the individual stacks of the Golgi apparatus are interconnected with each other and form a twisted ribbon-like network (Figure 3). However, in some cell lines, like MCF7, the Golgi apparatus is more fragmented and scattered throughout the cytosol, making it easier to distribute between daughter cells in mitosis. The shape of the Golgi ribbon is not necessary for its function in post-translational modifications nor in secretion. However, it has been suggested the the ribbon structure and its positioning close to the nucleus has a role in cell polarization, including polarized secretion and migration (Wei JH et al. (2010)).


YIPF3 - U2OS

YIPF3 - SH-SY5Y

YIPF3 - MCF-7

Figure 3. Examples of the morphology of the Golgi apparatus in different cell lines, represented by immunofluorescent staining of the protein encoded by YIPF3 in U2OS, SH-SY5Y, and MCF7 cells.


Figure 4. 3D-view of the Golgi apparatus in U2OS, visualized by immunofluorescent staining of GORASP2. The morphology of the Golgi apparatus in human induced stem cells can be seen in the Allen Cell Explorer.

The function of the Golgi apparatus

The Golgi apparatus is the key organelle in the secretory pathway and essential for the sorting and intracellular trafficking of proteins and membranes (Short B et al. (2000); Kulkarni-Gosavi P et al. (2019); Wilson C et al. (2011); Farquhar MG et al. (1998). Most newly synthesized proteins that enter the secretory pathway move from the ER through the Golgi apparatus to their final destination (Brandizzi F et al. (2013)). During transit through the Golgi apparatus they are heavily modified by post-translational modifications mediated by Golgi-resident proteins. These modifications include for exaMPLE glycosylation, sulfation, phosphorylation, and proteolytic cleavage. Such modifications are often important for the functional characteristics of the modified protein as well as for the proper sorting and transportation of the protein. Therefore, it is not surprising that malfunctions of Golgi-associated proteins that affect the morphology, the trafficking or post-translational modifications (especially glycosylation) that occur in the compartment, can lead to human diseases such as Congenital Disorder of Glycosylation (CDG) (Potelle S et al. (2015)).

Gene Ontology (GO)-based enrichment analysis of genes encoding proteins that localize to the Golgi apparatus reveals several functions associated with this organelle. The most highly enriched terms for the GO domain Biological Process are related to Golgi localization and organization, regulation of cell size, vesicle- and transmembrane transport, and posttranslational modifications of proteins (Figure 5a). Enrichment analysis of the GO domain Molecular Function reveals enrichment of genes with various enzymatic activities, and proteins related to SNAP receptors (SNARES) (Figure 5b). The latter play important roles in fusion of vesicles (Yoon TY et al. (2018)).

01234567891011Fold EnrichmentPositive regulation of cell ...Nucleotide-sugar transmembra...Protein localization to Golg...Golgi organizationEstablishment of protein loc...Golgi vesicle transportGlycoprotein biosynthetic pr...Cytosolic transportPlatelet degranulationProtein lipidationVesicle-mediated transport t...Regulation of response to wo...Negative regulation of neuro...Extracellular structure orga...Post-translational protein m...Modulation of chemical synap...Regulation of trans-synaptic...

Figure 5a. Gene Ontology-based enrichment analysis for the Golgi apparatus proteome showing the significantly enriched terms for the GO domain Biological Process. Each bar is clickable and gives a search result of proteins that belong to the selected category.

012345678Fold EnrichmentNitric-oxide synthase bindingAlpha-mannosidase activityProtein kinase A regulatory ...Phosphatidylinositol-4-phosp...Catalytic activity, acting o...SNAP receptor activitySulfotransferase activityTransferase activity, transf...SNARE bindingRab GTPase bindingPeptidase regulator activityCarbohydrate bindingReceptor ligand activity

Figure 5b. Gene Ontology-based enrichment analysis for the Golgi apparatus proteome showing the significantly enriched terms for the GO domain Molecular Function. Each bar is clickable and gives a search result of proteins that belong to the selected category.

Proteins that are involved in the maintenance of the Golgi apparatus are suitable markers of the Golgi apparatus, e.g. members of the Golgin protein family (Table 1). However, they do not belong to the group of proteins with the highest expression, which contains several proteins related to vesicle transport, such as CAV1 and COPE (Table 2).

Table 1. Selection of proteins suitable as markers for the Golgi apparatus.

Gene
Description
Substructure
GOLGB1 Golgin B1 Golgi apparatus
GOLGA5 Golgin A5 Golgi apparatus
GALNT2 Polypeptide N-acetylgalactosaminyltransferase 2 Golgi apparatus
ZFPL1 Zinc finger protein like 1 Golgi apparatus
GORASP2 Golgi reassembly stacking protein 2 Golgi apparatus
GOLM1 Golgi membrane protein 1 Golgi apparatus
GOLIM4 Golgi integral membrane protein 4 Golgi apparatus

Table 2. Highly expressed single localizing Golgi apparatus-associated proteins across different cell lines.

Gene
Description
Average nTPM
SPP1 Secreted phosphoprotein 1 391
SRGN Serglycin 300
CD74 CD74 molecule 242
RER1 Retention in endoplasmic reticulum sorting receptor 1 196
LMAN2 Lectin, mannose binding 2 157
COPE COPI coat complex subunit epsilon 156
SDF4 Stromal cell derived factor 4 142
TMED3 Transmembrane p24 trafficking protein 3 109
NUCB2 Nucleobindin 2 96
GALNT2 Polypeptide N-acetylgalactosaminyltransferase 2 95

Golgi apparatus-associated proteins with multiple locations

Approximately 79% (n=986) of the Golgi apparatus-associated proteins detected in the subcellular resource also localize to other compartments in the cell. The network plot (Figure 6) shows that dual locations between the Golgi apparatus and vesicles are overrepresented. This is in agreement with the interplay between the Golgi apparatus and vesicles in the secterory pathway. Figure 7 shows examples of the most common and/or overrepresented combinations for multilocalizing proteins in the proteome of the Golgi apparatus.

Figure 6. Interactive network plot of Golgi-associated proteins with multiple localizations. The numbers in the connecting nodes show the proteins that are localized to the Golgi apparatus and to one or more additional locations. Only connecting nodes containing at least 1.0% of proteins in the Golgi apparatus proteome are shown. The circle sizes are related to the number of proteins. The cyan colored nodes show combinations that are significantly overrepresented, while magenta colored nodes show combinations that are significantly underrepresented as compared to the probability of observing that combination based on the frequency of each annotation and a hypergeometric test (p≤0.05). Note that this calculation is only done for proteins with dual localizations. Each node is clickable and results in a list of all proteins that are found in the connected organelles.


SLC39A14 - A-431

RAB20 - U2OS

TMEM87A - A-431

Figure 7. Examples of multilocalizing proteins in the proteome of the Golgi apparatus. SLC39A14 is a zinc transporter that was identified in the Golgi apparatus, ER, and plasma membrane. It might be involved in the regulation of the zinc ion homeostasis (detected in A-431 cells). RAB20 is a protein that was identified in the Golgi apparatus as well as in cytoplasmic vesicles, and is involved in endocytosis (detected in U2OS cells). TMEM87A is a transmembrane protein whose subcellular location and function have not been described previously, but was detected in the Golgi apparatus and nucleoplasm (detected in A-431 cells).

Expression levels of Golgi apparatus-associated proteins in tissue

Transcriptome analysis and classification of genes into tissue distribution categories (Figure 8) shows that a significantly larger fraction of genes encoding Golgi apparatus-associated proteins are detected in many tissues, compared to all genes presented in the subcellular resource. Also, a slightly lower fraction of these genes belong to those not detected in any of the tissues that have been analyzed.

**Detected in singleDetected in someDetected in manyDetected in allNot detected0.0102030405060708090100%Golgi apparatusAll localized genes

Figure 8. Bar plot showing the percentage of genes in different tissue distribution categories for Golgi apparatus-associated protein-coding genes, compared to all genes in the subcellular resource. Asterisk marks a statistically significant deviation (p≤0.05) in the number of genes in a category based on a binomial statistical test. Each bar is clickable and gives a search result of proteins that belong to the selected category.

Relevant links and publications

Kulkarni-Gosavi P et al., Form and function of the Golgi apparatus: scaffolds, cytoskeleton and signalling. FEBS Lett. (2019)
PubMed: 31378930 DOI: 10.1002/1873-3468.13567

Short B et al., The Golgi apparatus. Curr Biol. (2000)
PubMed: 10985372 DOI: 10.1016/s0960-9822(00)00644-8

Wei JH et al., Unraveling the Golgi ribbon. Traffic. (2010)
PubMed: 21040294 DOI: 10.1111/j.1600-0854.2010.01114.x

Wilson C et al., The Golgi apparatus: an organelle with multiple complex functions. Biochem J. (2011)
PubMed: 21158737 DOI: 10.1042/BJ20101058

Farquhar MG et al., The Golgi apparatus: 100 years of progress and controversy. Trends Cell Biol. (1998)
PubMed: 9695800 

Brandizzi F et al., Organization of the ER-Golgi interface for membrane traffic control. Nat Rev Mol Cell Biol. (2013)
PubMed: 23698585 DOI: 10.1038/nrm3588

Potelle S et al., Golgi post-translational modifications and associated diseases. J Inherit Metab Dis. (2015)
PubMed: 25967285 DOI: 10.1007/s10545-015-9851-7

Yoon TY et al., SNARE complex assembly and disassembly. Curr Biol. (2018)
PubMed: 29689222 DOI: 10.1016/j.cub.2018.01.005