We use cookies to enhance the usability of our website. If you continue, we'll assume that you are happy to receive all cookies. More information. Don't show this again.
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 Cell Atlas, 1092 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 the Golgi apparatus proteome shows highly enriched terms for biological processes related to vesicle transport, zinc ion homeostasis, and glycosylation of proteins. Around 76% (n=826 proteins) of the Golgi apparatus proteins localize to one or more additional cellular compartments, the most common ones being nucleus, cytosol 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.
6% (1092 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 74 proteins are enhanced by the Human Protein Atlas.
826 proteins in the golgi apparatus have multiple locations.
148 proteins in the golgi apparatus show a cell to cell variation. Of these 141 show a variation in intensity and 7 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 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 E) 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) 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 tand the 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 (Brandizzi F et al. (2013)), sulfation, phosphorylation, and proteolytic cleavage. They are an important factor for the functional characteristics of the modified protein as well as for the proper sorting and transportation. 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 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 transportation. and posttranslational modifications 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.
Golgi apparatus-associated proteins with multiple locations
Approximately 76% (n=826) 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 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 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 be 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
Parikh K et al., Colonic epithelial cell diversity in health and inflammatory bowel disease.Nature. (2019)
PubMed: 30814735 DOI: 10.1038/s41586-019-0992-y
Menon M et al., Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration.Nat Commun. (2019)
PubMed: 31653841 DOI: 10.1038/s41467-019-12780-8
Wang L et al., Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function.Nat Cell Biol. (2020)
PubMed: 31915373 DOI: 10.1038/s41556-019-0446-7
Wang Y et al., Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine.J Exp Med. (2020)
PubMed: 31753849 DOI: 10.1084/jem.20191130
Liao J et al., Single-cell RNA sequencing of human kidney.Sci Data. (2020)
PubMed: 31896769 DOI: 10.1038/s41597-019-0351-8
MacParland SA et al., Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations.Nat Commun. (2018)
PubMed: 30348985 DOI: 10.1038/s41467-018-06318-7
Vieira Braga FA et al., A cellular census of human lungs identifies novel cell states in health and in asthma.Nat Med. (2019)
PubMed: 31209336 DOI: 10.1038/s41591-019-0468-5
Vento-Tormo R et al., Single-cell reconstruction of the early maternal-fetal interface in humans.Nature. (2018)
PubMed: 30429548 DOI: 10.1038/s41586-018-0698-6
Qadir MMF et al., Single-cell resolution analysis of the human pancreatic ductal progenitor cell niche.Proc Natl Acad Sci U S A. (2020)
PubMed: 32354994 DOI: 10.1073/pnas.1918314117
Solé-Boldo L et al., Single-cell transcriptomes of the human skin reveal age-related loss of fibroblast priming.Commun Biol. (2020)
PubMed: 32327715 DOI: 10.1038/s42003-020-0922-4
Henry GH et al., A Cellular Anatomy of the Normal Adult Human Prostate and Prostatic Urethra.Cell Rep. (2018)
PubMed: 30566875 DOI: 10.1016/j.celrep.2018.11.086
Chen J et al., PBMC fixation and processing for Chromium single-cell RNA sequencing.J Transl Med. (2018)
PubMed: 30016977 DOI: 10.1186/s12967-018-1578-4
Uhlen M et al., A proposal for validation of antibodies.Nat Methods. (2016)
PubMed: 27595404 DOI: 10.1038/nmeth.3995
Stadler C et al., Systematic validation of antibody binding and protein subcellular localization using siRNA and confocal microscopy.J Proteomics. (2012)
PubMed: 22361696 DOI: 10.1016/j.jprot.2012.01.030
Poser I et al., BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals.Nat Methods. (2008)
PubMed: 18391959 DOI: 10.1038/nmeth.1199
Skogs M et al., Antibody Validation in Bioimaging Applications Based on Endogenous Expression of Tagged Proteins.J Proteome Res. (2017)
PubMed: 27723985 DOI: 10.1021/acs.jproteome.6b00821
Takahashi H et al., 5' end-centered expression profiling using cap-analysis gene expression and next-generation sequencing.Nat Protoc. (2012)
PubMed: 22362160 DOI: 10.1038/nprot.2012.005
Lein ES et al., Genome-wide atlas of gene expression in the adult mouse brain.Nature. (2007)
PubMed: 17151600 DOI: 10.1038/nature05453
Kircher M et al., Double indexing overcomes inaccuracies in multiplex sequencing on the Illumina platform.Nucleic Acids Res. (2012)
PubMed: 22021376 DOI: 10.1093/nar/gkr771
Pollard TD et al., Actin, a central player in cell shape and movement.Science. (2009)
PubMed: 19965462 DOI: 10.1126/science.1175862
Mitchison TJ et al., Actin-based cell motility and cell locomotion.Cell. (1996)
PubMed: 8608590
dos Remedios CG et al., Actin binding proteins: regulation of cytoskeletal microfilaments.Physiol Rev. (2003)
PubMed: 12663865 DOI: 10.1152/physrev.00026.2002
Campellone KG et al., A nucleator arms race: cellular control of actin assembly.Nat Rev Mol Cell Biol. (2010)
PubMed: 20237478 DOI: 10.1038/nrm2867
Rottner K et al., Actin assembly mechanisms at a glance.J Cell Sci. (2017)
PubMed: 29032357 DOI: 10.1242/jcs.206433
Bird RP., Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings.Cancer Lett. (1987)
PubMed: 3677050 DOI: 10.1016/0304-3835(87)90157-1
HUXLEY AF et al., Structural changes in muscle during contraction; interference microscopy of living muscle fibres.Nature. (1954)
PubMed: 13165697
HUXLEY H et al., Changes in the cross-striations of muscle during contraction and stretch and their structural interpretation.Nature. (1954)
PubMed: 13165698
Svitkina T., The Actin Cytoskeleton and Actin-Based Motility.Cold Spring Harb Perspect Biol. (2018)
PubMed: 29295889 DOI: 10.1101/cshperspect.a018267
Kelpsch DJ et al., Nuclear Actin: From Discovery to Function.Anat Rec (Hoboken). (2018)
PubMed: 30312531 DOI: 10.1002/ar.23959
Malumbres M et al., Cell cycle, CDKs and cancer: a changing paradigm.Nat Rev Cancer. (2009)
PubMed: 19238148 DOI: 10.1038/nrc2602
Massagué J., G1 cell-cycle control and cancer.Nature. (2004)
PubMed: 15549091 DOI: 10.1038/nature03094
Hartwell LH et al., Cell cycle control and cancer.Science. (1994)
PubMed: 7997877 DOI: 10.1126/science.7997877
Cho RJ et al., Transcriptional regulation and function during the human cell cycle.Nat Genet. (2001)
PubMed: 11137997 DOI: 10.1038/83751
Whitfield ML et al., Identification of genes periodically expressed in the human cell cycle and their expression in tumors.Mol Biol Cell. (2002)
PubMed: 12058064 DOI: 10.1091/mbc.02-02-0030.
Boström J et al., Comparative cell cycle transcriptomics reveals synchronization of developmental transcription factor networks in cancer cells.PLoS One. (2017)
PubMed: 29228002 DOI: 10.1371/journal.pone.0188772
Lane KR et al., Cell cycle-regulated protein abundance changes in synchronously proliferating HeLa cells include regulation of pre-mRNA splicing proteins.PLoS One. (2013)
PubMed: 23520512 DOI: 10.1371/journal.pone.0058456
Ohta S et al., The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics.Cell. (2010)
PubMed: 20813266 DOI: 10.1016/j.cell.2010.07.047
Ly T et al., A proteomic chronology of gene expression through the cell cycle in human myeloid leukemia cells.Elife. (2014)
PubMed: 24596151 DOI: 10.7554/eLife.01630
Pagliuca FW et al., Quantitative proteomics reveals the basis for the biochemical specificity of the cell-cycle machinery.Mol Cell. (2011)
PubMed: 21816347 DOI: 10.1016/j.molcel.2011.05.031
Ly T et al., Proteomic analysis of the response to cell cycle arrests in human myeloid leukemia cells.Elife. (2015)
PubMed: 25555159 DOI: 10.7554/eLife.04534
Dueck H et al., Variation is function: Are single cell differences functionally important?: Testing the hypothesis that single cell variation is required for aggregate function.Bioessays. (2016)
PubMed: 26625861 DOI: 10.1002/bies.201500124
Snijder B et al., Origins of regulated cell-to-cell variability.Nat Rev Mol Cell Biol. (2011)
PubMed: 21224886 DOI: 10.1038/nrm3044
Cooper S et al., Membrane-elution analysis of content of cyclins A, B1, and E during the unperturbed mammalian cell cycle.Cell Div. (2007)
PubMed: 17892542 DOI: 10.1186/1747-1028-2-28
Davis PK et al., Biological methods for cell-cycle synchronization of mammalian cells.Biotechniques. (2001)
PubMed: 11414226 DOI: 10.2144/01306rv01
Domenighetti G et al., Effect of information campaign by the mass media on hysterectomy rates.Lancet. (1988)
PubMed: 2904581 DOI: 10.1016/s0140-6736(88)90943-9
Scialdone A et al., Computational assignment of cell-cycle stage from single-cell transcriptome data.Methods. (2015)
PubMed: 26142758 DOI: 10.1016/j.ymeth.2015.06.021
Sakaue-Sawano A et al., Visualizing spatiotemporal dynamics of multicellular cell-cycle progression.Cell. (2008)
PubMed: 18267078 DOI: 10.1016/j.cell.2007.12.033
Grant GD et al., Identification of cell cycle-regulated genes periodically expressed in U2OS cells and their regulation by FOXM1 and E2F transcription factors.Mol Biol Cell. (2013)
PubMed: 24109597 DOI: 10.1091/mbc.E13-05-0264
Semple JW et al., An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes.EMBO J. (2006)
PubMed: 17053779 DOI: 10.1038/sj.emboj.7601391
Kilfoil ML et al., Stochastic variation: from single cells to superorganisms.HFSP J. (2009)
PubMed: 20514130 DOI: 10.2976/1.3223356
Ansel J et al., Cell-to-cell stochastic variation in gene expression is a complex genetic trait.PLoS Genet. (2008)
PubMed: 18404214 DOI: 10.1371/journal.pgen.1000049
Colman-Lerner A et al., Regulated cell-to-cell variation in a cell-fate decision system.Nature. (2005)
PubMed: 16170311 DOI: 10.1038/nature03998
Liberali P et al., Single-cell and multivariate approaches in genetic perturbation screens.Nat Rev Genet. (2015)
PubMed: 25446316 DOI: 10.1038/nrg3768
Elowitz MB et al., Stochastic gene expression in a single cell.Science. (2002)
PubMed: 12183631 DOI: 10.1126/science.1070919
Kaern M et al., Stochasticity in gene expression: from theories to phenotypes.Nat Rev Genet. (2005)
PubMed: 15883588 DOI: 10.1038/nrg1615
Bianconi E et al., An estimation of the number of cells in the human body.Ann Hum Biol. (2013)
PubMed: 23829164 DOI: 10.3109/03014460.2013.807878
Collins K et al., The cell cycle and cancer.Proc Natl Acad Sci U S A. (1997)
PubMed: 9096291
Zhivotovsky B et al., Cell cycle and cell death in disease: past, present and future.J Intern Med. (2010)
PubMed: 20964732 DOI: 10.1111/j.1365-2796.2010.02282.x
Cho RJ et al., A genome-wide transcriptional analysis of the mitotic cell cycle.Mol Cell. (1998)
PubMed: 9702192
Spellman PT et al., Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization.Mol Biol Cell. (1998)
PubMed: 9843569
Orlando DA et al., Global control of cell-cycle transcription by coupled CDK and network oscillators.Nature. (2008)
PubMed: 18463633 DOI: 10.1038/nature06955
Rustici G et al., Periodic gene expression program of the fission yeast cell cycle.Nat Genet. (2004)
PubMed: 15195092 DOI: 10.1038/ng1377
Nigg EA et al., The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries.Nat Cell Biol. (2011)
PubMed: 21968988 DOI: 10.1038/ncb2345
Conduit PT et al., Centrosome function and assembly in animal cells.Nat Rev Mol Cell Biol. (2015)
PubMed: 26373263 DOI: 10.1038/nrm4062
Tollenaere MA et al., Centriolar satellites: key mediators of centrosome functions.Cell Mol Life Sci. (2015)
PubMed: 25173771 DOI: 10.1007/s00018-014-1711-3
Prosser SL et al., Centriolar satellite biogenesis and function in vertebrate cells.J Cell Sci. (2020)
PubMed: 31896603 DOI: 10.1242/jcs.239566
Rieder CL et al., The centrosome in vertebrates: more than a microtubule-organizing center.Trends Cell Biol. (2001)
PubMed: 11567874
Badano JL et al., The centrosome in human genetic disease.Nat Rev Genet. (2005)
PubMed: 15738963 DOI: 10.1038/nrg1557
Clegg JS., Properties and metabolism of the aqueous cytoplasm and its boundaries.Am J Physiol. (1984)
PubMed: 6364846
Luby-Phelps K., The physical chemistry of cytoplasm and its influence on cell function: an update.Mol Biol Cell. (2013)
PubMed: 23989722 DOI: 10.1091/mbc.E12-08-0617
Luby-Phelps K., Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area.Int Rev Cytol. (2000)
PubMed: 10553280
Bright GR et al., Fluorescence ratio imaging microscopy: temporal and spatial measurements of cytoplasmic pH.J Cell Biol. (1987)
PubMed: 3558476
Kopito RR., Aggresomes, inclusion bodies and protein aggregation.Trends Cell Biol. (2000)
PubMed: 11121744
Aizer A et al., Intracellular trafficking and dynamics of P bodies.Prion. (2008)
PubMed: 19242093
Carcamo WC et al., Molecular cell biology and immunobiology of mammalian rod/ring structures.Int Rev Cell Mol Biol. (2014)
PubMed: 24411169 DOI: 10.1016/B978-0-12-800097-7.00002-6
Lang F., Mechanisms and significance of cell volume regulation.J Am Coll Nutr. (2007)
PubMed: 17921474
Schwarz DS et al., The endoplasmic reticulum: structure, function and response to cellular signaling.Cell Mol Life Sci. (2016)
PubMed: 26433683 DOI: 10.1007/s00018-015-2052-6
Friedman JR et al., The ER in 3D: a multifunctional dynamic membrane network.Trends Cell Biol. (2011)
PubMed: 21900009 DOI: 10.1016/j.tcb.2011.07.004
Travers KJ et al., Functional and genomic analyses reveal an essential coordination between the unfolded protein response and ER-associated degradation.Cell. (2000)
PubMed: 10847680
Roussel BD et al., Endoplasmic reticulum dysfunction in neurological disease.Lancet Neurol. (2013)
PubMed: 23237905 DOI: 10.1016/S1474-4422(12)70238-7
Neve EP et al., Cytochrome P450 proteins: retention and distribution from the endoplasmic reticulum.Curr Opin Drug Discov Devel. (2010)
PubMed: 20047148
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
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