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 morphological distinct architecture. It consists of stacks of
interconnected membrane cisternae, and resides close to the nucleus in the 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, 984 (5%) have been experimentally shown to localize to the Golgi apparatus
(Figure 2). 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 74% (730 proteins) of the Golgi apparatus proteins localize to one or more additional cellular compartments, the most common ones being nucleus, cytosol and vesicles.
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% (984 proteins) of all human proteins have been experimentally detected in the Golgi apparatus by the Human Protein Atlas.
- 283 proteins in the Golgi apparatus are supported by experimental evidence and out of these 75 proteins are enhanced by the Human Protein Atlas.
- 730 proteins in the Golgi apparatus have multiple locations.
- 92 proteins in the Golgi apparatus show a cell to cell variation. Of these 87 show a variation in intensity and 5 a spatial variation.
- Proteins are mainly involved in protein transport and modification.
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 a 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 they are interconnected with each other and
form a twisted ribbon-like network (Figure 3). This structure of the Golgi apparatus is only present in vertebrates, yet this shape is not
necessary for its function of post-translational modifications or secretion. Plants and other organism as well as some human cell lines like
MCF7 have a more fragmented Golgi apparatus shattered throughout the cytosol. Hence, in vertebrates this structure as well as the positioning
close to the nucleus might be involved in other processes such as the regulation of the cell's entry into mitosis
(Wei and Seemann, 2010).
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.
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), or 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
(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 4a). Enrichment analysis of
the GO domain Molecular Function shows the terms phosphatidylinositol-4-phosphate binding and SNAP receptor activity, which includes proteins for
protein sorting and transportation or mediate fusion between Golgi-membrane and vesicles (Figure 4b).
Figure 4.a 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 4.b 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
RAB6A (Table 2).
Table 1. Selection of proteins suitable as markers for the Golgi apparatus.
||Polypeptide N-acetylgalactosaminyltransferase 2
||Zinc finger protein like 1
||Golgi reassembly stacking protein 2
||Golgi membrane protein 1
||Golgi integral membrane protein 4
Table 2. Highly expressed single localizing Golgi apparatus-associated proteins across different cell lines.
||Secreted phosphoprotein 1
||Retention in endoplasmic reticulum sorting receptor 1
||Coatomer protein complex subunit epsilon
||Stromal cell derived factor 4
||Transmembrane p24 trafficking protein 10
||Family with sequence similarity 3 member C
||Transmembrane p24 trafficking protein 3
Golgi apparatus-associated proteins with multiple locations
Approximately 74% (n=730) 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 of Golgi apparatus with other organelles of the secretory pathway, ER and vesicles,
as well as with nucleoplasm are overrepresented.
The examples in Figure 6 show common 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.
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
The transcriptome analysis (Figure 7) shows that genes encoding for Golgi apparatus-associated proteins are not significantly
differently expressed than other genes.
Figure 7. Bar plot showing the distribution of expression categories, based on the gene expression in tissues, for Golgi apparatus-associated protein-coding genes compared to all genes in the Cell Atlas. Each bar is clickable and gives a search result of proteins that belong to the selected category.
Relevant links and publications
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.
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.
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