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, being involved in the post-translational modification, packaging and sorting of proteins.
In the Subcellular Section, 1127 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 protein that localize to the Golgi apparatus mostly shows enrichment of terms related to transmembrane- and vesicle transportation, as well as protein metabolism and processing. Around 76% (n=853 proteins) of the Golgi apparatus proteins localize to one or more additional cellular compartments, the most common ones being nucleus and vesicles. Examples of Golgi-associated proteins can be found in Figure 1.
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).
6% (1127 proteins) of all human proteins have been experimentally detected in the golgi apparatus by the Human Protein Atlas.
271 proteins in the golgi apparatus are supported by experimental evidence and out of these 72 proteins are enhanced by the Human Protein Atlas.
853 proteins in the golgi apparatus have multiple locations.
156 proteins in the golgi apparatus show a cell to cell variation. Of these 151 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. 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)).
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
The Golgi apparatus is the key organelle in the secretory pathway and essential for the 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, but are not limited to, 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 of the Golgi apparatus, or 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, vesicle- and transmembrane transportation, and posttranslational modifications of proteins (Figure 5a). Enrichment analysis of the GO domain Molecular Function points towards enrichment of genes with various enzymatic activities, and proteins that form or bind to SNAP receptors (SNARES) (Figure 5b). The latter play important roles in fusion of vesicles (Yoon TY et al. (2018)).
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, 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.
Golgi apparatus-associated proteins with multiple locations
Approximately 76% (n=853) of the Golgi apparatus-associated proteins detected in the Subcellular Section 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 ER, are overrepresented. This is in agreement with the interplay between the ER, Golgi and vesicles in the secterory pathway. However, there is also an over-representation of genes that localize to the Golgi apparatus and the nucleus. Figure 6 shows 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.
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 U-2 OS 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 7) shows that genes encoding Golgi apparatus-associated proteins have a similar distribution over these categories as for all genes presented in the Subcellular Section, with the exception that a slightly lower fraction of these genes belong to those not detected in any of the tissues that have been analyzed.
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 Section. 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.
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