Cytosol

The cytosol is a semi-fluid substance filling the interior of the cell and embedding the other organelles and subcellular compartments (Clegg JS. (1984)). The cytosol itself is enclosed by the cell membrane and the membranes of different organelles, thus making up a separate cellular compartment. Together, the cytosol and all organelles, except for the nucleus, make up the cytoplasm. Example images of proteins localized to the cytosol can be seen in Figure 1.

In the Subcellular Section, 4889 genes (24% of all protein-coding human genes) have been shown to encode proteins that localize to the cytosol and its substructures (Figure 2). Analysis of the cytosolic proteome shows enrichment of terms for biological processes related to protein modification, mRNA degradation, metabolic processes, signal transduction, and cell death. About 79% (n=3865) of the cytosolic proteins localize to other cellular compartments in addition to the cytosol. The most common additional locations are the nucleus and the plasma membrane.

G3BP1 - U-251 MG
QARS1 - U-2 OS
MTHFS - U-2 OS

Figure 1. Examples of proteins localized to the cytosol. G3BP1 is an enzyme localized in the cytosol and plays a role in signal transduction (detected in U-251 MG cells). QARS1 catalyzes the aminoacylation of tRNA by their associated amino acid (detected in U-2 OS cells). MTHFS is an enzyme involved in metabolic processes (detected in U-2 OS cells).

Figure 2. 24% of all human protein-coding genes encode proteins localized to the cytosol. Each bar is clickable and gives a search result of proteins that belong to the selected category.

Composition of the cytosol

Substructures

• Aggresome: 20
• Cytosol: 4813
• Cytoplasmic bodies: 73
• Rods & Rings: 19

The cytosol makes up about 70% of the total volume of human cells, and is highly crowded and complex (Luby-Phelps K. (2013)). The cytosol is mainly composed of water (approximately 70% of the volume) and proteins (20-30% of the volume) (Luby-Phelps K. (2000); Ellis RJ. (2001)). Rather than a liquid, it is often described as a hydrophilic jelly-like matrix that allows for free movement of ions, hydrophilic molecules and proteins, but also larger structures such as protein complexes and vesicles, across the cell. Ions such as potassium, sodium, bicarbonate, chloride, calcium, magnesium and amino acids are also important constitues of the cytosol. The differences in concentration of these ions between the cytosol and the extracellular fluid or cytoplamic organelles are essential for many cellular functions, for example to enable cell-to-cell communication at the synapses of nerve cells. Human cytosolic pH ranges between 7.0 - 7.4 and is usually higher if the cell is growing (Bright GR et al. (1987)).

Example images of the protein coded by MTHFD1 stained in 3 different cell lines can be seen in Figure 3.

MTHFD1 - A-431
MTHFD1 - U-251 MG
MTHFD1 - U-2 OS

Figure 3. Examples of the morphology of the cytosol in different cell lines, represented by immunofluorescent staining of protein MTHFD1 in A-431, U-251 MG and U-2 OS cells.

The cytosol also contains different non-membrane bound structures, including cytoplasmic inclusions, such as glycogen-, pigment- and crystalline inclusions, and cytoplasmic bodies, such as P-bodies and stress granules. Aggresomes are large inclusion bodies formed upon active retrograde transport of misfolded proteins along microtubules (Kopito RR. (2000)). This sequestration of aggregated proteins that fail to be cleared by proteosomal degradation has a cytoprotective function. P-bodies are non-membrane bound foci of mRNA and proteins that function in RNA turnover, translational repression, RNA-mediated silencing, and RNA storage (Aizer A et al. (2008)). A rare, and rather recently discovered structure that can appear in the cytosol are Rods and Rings (RRs). These are filament-like structures containing proteins involved in the biosynthesis of nucleotides, originally discovered by the use of human autoantibodies, but little is known about their biological function (Carcamo WC et al. (2014)).

A selection of proteins suitable to be used as markers for the cytosol is listed in Table 1.

Table 1. Selection of proteins suitable as markers for the cytosol.

Gene	Description	Substructure
ADSL	Adenylosuccinate lyase	Cytosol
ATXN2	Ataxin 2	Cytosol
G3BP2	G3BP stress granule assembly factor 2	Cytosol
AIMP1	Aminoacyl tRNA synthetase complex interacting multifunctional protein 1	Cytosol
SERBP1	SERPINE1 mRNA binding protein 1	Cytosol
CCDC43	Coiled-coil domain containing 43	Cytosol
ATXN2L	Ataxin 2 like	Cytosol
AMPD2	Adenosine monophosphate deaminase 2	Cytosol
RABGAP1	RAB GTPase activating protein 1	Cytosol

Function of the cytosol

The cytosol has an important role in providing structural support for other organelles and in allowing transport of molecules across the cell. For example, metabolites often need to be transported across the cytosol from the area of their production to the site where they are needed, and various signals need to be transduced from the cell membrane to target compartments. Moreover, many important cellular processes and reactions, especially of metabolic character, occur in the cytosol. These processes include protein synthesis through translation, the first stage of cellular respiration through glycolysis, and cell division through mitosis and meiosis. The cytosol also plays a pivotal role in maintaining gradients across the membranes, which is important for cell signalling, osmosis and cellular excitability (Lang F. (2007)).

A list of highly expressed cytosolic proteins is summarized in Table 2. Gene Ontology (GO)-based analysis of the cytosolic proteome shows enrichment of terms that are well in-line with the known functions of the cytosol. The most highly enriched terms for the GO domain Biological Process are related to translation, post-translational modifications, metabolic pathways, signaling pathways, and apoptosis (Figure 4a). Enrichment analysis of the GO domain Molecular Function also shows significant enrichment for terms related to translation, protein metabolism and cell cignalling(Figure 4b).

Figure 4a. Gene Ontology-based enrichment analysis for the cytosol 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 4b. Gene Ontology-based enrichment analysis for the cytosol 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.

Table 2. Highly expressed single localizing cytosolic proteins across different cell lines.

Gene	Description	Average nTPM
RPS18	Ribosomal protein S18	6512
TPT1	Tumor protein, translationally-controlled 1	4067
RPL23	Ribosomal protein L23	2672
CFL1	Cofilin 1	1777
PKM	Pyruvate kinase M1/2	1737
HSP90AB1	Heat shock protein 90 alpha family class B member 1	1654
HSP90AA1	Heat shock protein 90 alpha family class A member 1	1381
LDHB	Lactate dehydrogenase B	1353
BTF3	Basic transcription factor 3	1132
PABPC1	Poly(A) binding protein cytoplasmic 1	913

Cytosol proteins with multiple locations

Approximately 79% (n=3865) of the cytosolic proteins detected in the Human Protein Atlas also localize to other cellular compartments (Figure 5). The network plot shows that the most common compartments sharing proteins with the cytosol are the nucleus, the plasma membrane and vesicles. Especially proteins that localize to both the cytosol and the nucleus, as well as the cytosol and the plasma membrane, are overrepresented. Indeed, there are many proteins known to be transported, or to continuously shuttle, between the cytosol and these compartments, including transcription factors, ribosomal proteins and signalling molecules. Examples of multilocalizing proteins within the cytosolic proteome can be seen in Figure 6.

Figure 5. Interactive network plot of the cytosol proteins with multiple localizations. The numbers in the connecting nodes show the proteins that are localized to the cytosol and to one or more additional locations. Only connecting nodes containing more than one protein and at least 0.5% of proteins in the cytosolic 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.

RPL10A - U-2 OS
STAT5A - A-431
DDX55 - A-431

Figure 6. Examples of multilocalizing proteins in the cytosolic proteome. RPL10A is a known ribosomal protein, which is required for formation of the 60S ribosomal subunits. It has been shown to localize both to the nucleoli and the cytosol (detected in U-2 OS cells). STAT5A belongs to the family of STAT transcription factors. It translocates from the cytosol into the nucleus in response to phosphorylation (detected in A-431 cells). DDX55 is a member of DEAD box protein family implicated in several cellular processes involving alteration of RNA secondary structure. It has been shown to localize to the nucleus, nucleoli and cytosol (detected in A-431 cells).

Expression levels of cytosol proteins in tissue

Transcriptome analysis and classification of genes into tissue distribution categories (Figure 8) shows that genes encoding proteins localizing to the cytosol and its substructures have a similar distribution as all genes in the Subcellular Section, but with a slightly larger fraction of genes expressed in all tissues, and a slightly smaller fraction of genes expressed in many tissues.

Figure 7. Bar plot showing the percentage of genes in different tissue distribution categories for cytosol-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.

Relevant links and publications

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

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

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

Guo J et al., The adult human testis transcriptional cell atlas. Cell Res. (2018)
PubMed: 30315278 DOI: 10.1038/s41422-018-0099-2

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

Lukassen S et al., SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells. EMBO J. (2020)
PubMed: 32246845 DOI: 10.15252/embj.20105114

Wang W et al., Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle. Nat Med. (2020)
PubMed: 32929266 DOI: 10.1038/s41591-020-1040-z

De Micheli AJ et al., A reference single-cell transcriptomic atlas of human skeletal muscle tissue reveals bifurcated muscle stem cell populations. Skelet Muscle. (2020)
PubMed: 32624006 DOI: 10.1186/s13395-020-00236-3

Man L et al., Comparison of Human Antral Follicles of Xenograft versus Ovarian Origin Reveals Disparate Molecular Signatures. Cell Rep. (2020)
PubMed: 32783948 DOI: 10.1016/j.celrep.2020.108027

Hildreth AD et al., Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol. (2021)
PubMed: 33907320 DOI: 10.1038/s41590-021-00922-4

He S et al., Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs. Genome Biol. (2020)
PubMed: 33287869 DOI: 10.1186/s13059-020-02210-0

Bhat-Nakshatri P et al., A single-cell atlas of the healthy breast tissues reveals clinically relevant clusters of breast epithelial cells. Cell Rep Med. (2021)
PubMed: 33763657 DOI: 10.1016/j.xcrm.2021.100219

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

Uhlén M et al., The human secretome. Sci Signal. (2019)
PubMed: 31772123 DOI: 10.1126/scisignal.aaz0274

Uhlen M et al., A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science. (2019)
PubMed: 31857451 DOI: 10.1126/science.aax9198

Sjöstedt E et al., An atlas of the protein-coding genes in the human, pig, and mouse brain. Science. (2020)
PubMed: 32139519 DOI: 10.1126/science.aay5947

Robinson JL et al., An atlas of human metabolism. Sci Signal. (2020)
PubMed: 32209698 DOI: 10.1126/scisignal.aaz1482

Uhlen M et al., A pathology atlas of the human cancer transcriptome. Science. (2017)
PubMed: 28818916 DOI: 10.1126/science.aan2507

Hikmet F et al., The protein expression profile of ACE2 in human tissues. Mol Syst Biol. (2020)
PubMed: 32715618 DOI: 10.15252/msb.20209610

Gordon DE et al., A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. (2020)
PubMed: 32353859 DOI: 10.1038/s41586-020-2286-9

Karlsson M et al., A single-cell type transcriptomics map of human tissues. Sci Adv. (2021)
PubMed: 34321199 DOI: 10.1126/sciadv.abh2169

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 

Pollard TD et al., Molecular Mechanism of Cytokinesis. Annu Rev Biochem. (2019)
PubMed: 30649923 DOI: 10.1146/annurev-biochem-062917-012530

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

Barnum KJ et al., Cell cycle regulation by checkpoints. Methods Mol Biol. (2014)
PubMed: 24906307 DOI: 10.1007/978-1-4939-0888-2_2

Weinberg RA., The retinoblastoma protein and cell cycle control. Cell. (1995)
PubMed: 7736585 DOI: 10.1016/0092-8674(95)90385-2

Morgan DO., Principles of CDK regulation. Nature. (1995)
PubMed: 7877684 DOI: 10.1038/374131a0

Teixeira LK et al., Ubiquitin ligases and cell cycle control. Annu Rev Biochem. (2013)
PubMed: 23495935 DOI: 10.1146/annurev-biochem-060410-105307

King RW et al., How proteolysis drives the cell cycle. Science. (1996)
PubMed: 8939846 DOI: 10.1126/science.274.5293.1652

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

Mahdessian D et al., Spatiotemporal dissection of the cell cycle with single-cell proteogenomics. Nature. (2021)
PubMed: 33627808 DOI: 10.1038/s41586-021-03232-9

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

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

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

Malumbres M., Cyclin-dependent kinases. Genome Biol. (2014)
PubMed: 25180339 

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

Uhlén M et al., Tissue-based map of the human proteome. Science (2015)
PubMed: 25613900 DOI: 10.1126/science.1260419

Nigg EA et al., The centrosome cycle: Centriole biogenesis, duplication and inherent asymmetries. Nat Cell Biol. (2011)
PubMed: 21968988 DOI: 10.1038/ncb2345

Doxsey S., Re-evaluating centrosome function. Nat Rev Mol Cell Biol. (2001)
PubMed: 11533726 DOI: 10.1038/35089575

Bornens M., Centrosome composition and microtubule anchoring mechanisms. Curr Opin Cell Biol. (2002)
PubMed: 11792541 

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 

Ellis RJ., Macromolecular crowding: obvious but underappreciated. Trends Biochem Sci. (2001)
PubMed: 11590012 

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