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 microtubule organizing centers. It plays a central role in the intracellular transport of 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, as they are involved in the post-translational modification, packaging and sorting of proteins.

The biological function of an organelle is defined by its proteome (see Figure 1 for examples of Golgi-associated proteins). Of all human proteins, 1030 (5%) have been experimentally shown to localize to the Golgi apparatus (Figure 2). A Gene Ontology (GO)-based functional enrichment analysis of the Golgi apparatus proteome shows highly enriched terms for biological processes related to vesicle transport, zinc ion homeostasis, and glycosylation of proteins. Around 75% (n=774 proteins) of the Golgi apparatus proteins localize to one or more additional cellular compartments, the most common ones being nucleus, cytosol and vesicles.


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.

  • 5% (1030 proteins) of all human proteins have been experimentally detected in the golgi apparatus by the Human Protein Atlas.
  • 285 proteins in the golgi apparatus are supported by experimental evidence and out of these 75 proteins are enhanced by the Human Protein Atlas.
  • 774 proteins in the golgi apparatus have multiple locations.
  • 111 proteins in the golgi apparatus show a cell to cell variation. Of these 106 show a variation in intensity and 5 a spatial variation.

  • Proteins localizing to the Golgi apparatus are mainly involved in transport and modification of proteins.

Figure 2. 5% 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

The individual membrane disks (called cisternae) of the Golgi apparatus are named after the direction in which proteins move through them. Proteins coming from the endoplasmatic reticulum (ER) or from the ER-Golgi intermediate compartment (ERGIC) enter in the cis-Golgi, followed by the medial- and the trans-Golgi, and ultimately exit via the adjacent Trans-Golgi-Network (TGN) to their final destination. The Golgi-membranes are characterized by constant emergence and fusion of small transport vesicles trafficking between the compartments.

The individual stacks of the Golgi apparatus are not isolated from each other in vertebrates, but rather interconnected with each other and form a twisted ribbon-like network (Figure 3). This structure of the Golgi apparatus is only present in the intephase of vertebran cells, while plants other organisms as well as some human cell lines like MCF7 have a more fragmented Golgi apparatus that is shattered 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 tand the positioning close to the nucleus has a role in cell polarization, including polarized secretion and migration (Wei and Seemann, 2010).

YIPF3 - U-2 OS



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 U-2 OS, SH-SY5Y, and MCF7 cells.

Figure 4. 3D-view of the Golgi apparatus in U-2 OS, 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

In its function as the key organelle in the secretory pathway, the Golgi apparatus is essential for the intracellular trafficking of proteins and membranes. Most newly synthesized proteins that enter the secretory pathway move from the ER through the Golgi apparatus to their final destination (Brandizzi and Barlowe, 2013). They are heavily post-translationally modified during their transit by Golgi-resident proteins. These modifications include but are not limited to glycosylation (Stanley P, 2011), sulfation (Hartmann-Fatu et al, 2015), phosphorylation (Tagliabracci et al, 2012), and proteolytic cleavage (Molloy et al, 1992). They are an important factor for the functional characteristics of the modified protein as well as for the proper sorting and transportation (Farquhar and Palade, 1998). Therefore, it is not surprising that malfunctions of Golgi-associated proteins that affect the morphology of the Golgi apparatus, the trafficking or post-translational modifications (especially glycosylation) can lead to human diseases such as Congenital Disorder of Glycosylation (CDG) (Potelle et al, 2015).

Gene Ontology (GO)-based enrichment analysis of genes encoding proteins that localize mainly 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 vesicle transportation and glycosylation of proteins, but also zinc ion homeostasis, pointing out the function of the Golgi apparatus as zinc ion storage (Figure 5a). Enrichment analysis of the GO domain Molecular Function shows the terms phosphatidylinositol-4-phosphate binding and SNAP receptor activity, which includes proteins involved in protein sorting and transportation, or membrane between the Golgi apparatus and vesicles (Figure 5b).

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.

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, that contains several proteins related to vesicle transport, such as CAV1, COPE, or RAB6A (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 NX
RER1 Retention in endoplasmic reticulum sorting receptor 1 39
SDF4 Stromal cell derived factor 4 32
COPE Coatomer protein complex subunit epsilon 32
CAV1 Caveolin 1 29
TMED10 Transmembrane p24 trafficking protein 10 26
SRGN Serglycin 24
TMED3 Transmembrane p24 trafficking protein 3 23
ATP2C1 ATPase secretory pathway Ca2+ transporting 1 22
ARFGAP2 ADP ribosylation factor GTPase activating protein 2 22
PI4KB Phosphatidylinositol 4-kinase beta 22

Golgi apparatus-associated proteins with multiple locations

Approximately 75% (n=774) of the Golgi apparatus-associated proteins detected in the Cell Atlas also localize to other compartments in the cell. The network plot (Figure 5) shows that dual locations between the Golgi apparatus and vesicles, as well as the nucleoplasm, are overrepresented. The former is in agreement with the close connection between the Golgi apparatus and vesicles in the secretory pathway. Figure 6 show examples of the most common and/or overrepresented combinations for multilocalizing proteins in the proteome of the Golgi apparatus.

Figure 5. 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 more than one protein and at least 0.5% 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 - U-2 OS

TMEM87A - A-431

Figure 6. 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 A-431 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 U-2 OS cells).

Expression levels of Golgi apparatus-associated proteins in tissue

Transcriptome analysis and classification of genes into tissue distribution categories (Figure 7) shows that genes encoding Golgi apparatus-associated proteins are less likely to de detected in all tissues but more likely to be detected in many tissues, compared to all genes presented in the Cell Atlas.

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 Cell Atlas. 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

Thul PJ et al, 2017. A subcellular map of the human proteome. Science.
PubMed: 28495876 DOI: 10.1126/science.aal3321

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

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

Hartmann-Fatu C et al, 2015. Heterodimers of tyrosylprotein sulfotransferases suggest existence of a higher organization level of transferases in the membrane of the trans-Golgi apparatus. J Mol Biol.
PubMed: 25660941 DOI: 10.1016/j.jmb.2015.01.021

Molloy SS et al, 1992. Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen. J Biol Chem.
PubMed: 1644824 

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

Stanley P. 2011. Golgi glycosylation. Cold Spring Harb Perspect Biol.
PubMed: 21441588 DOI: 10.1101/cshperspect.a005199

Tagliabracci VS et al, 2012. Secreted kinase phosphorylates extracellular proteins that regulate biomineralization. Science.
PubMed: 22582013 DOI: 10.1126/science.1217817

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