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.
Wagner and Valentin were the first to describe the nucleolus in two independent publications in the 1830s. The nucleolus is a nuclear sub-compartment that varies in size and number depending on cell type. The main function of the nucleolus is to synthesize and assemble ribosomes for later transport to the cytoplasm, where translation takes place. The nucleolus is also involved in cell cycle regulation and cellular stress responses. Example images of proteins localized to the nucleoli can be seen in Figure 1.
In the Subcellular Section, 1410 genes (7% of all protein-coding human genes) have been shown to encode proteins that localize to nucleoli (Figure 2). A Gene Ontology (GO)-based functional enrichment analysis of the nucleolar proteins shows enrichment of terms for biological processes related to rRNA processing. Approximately 88% (n=1245) of the nucleolar proteins localize to other cellular compartments in addition to nucleoli, with 35% (n=489) only localizing to other nuclear compartments. The most common additional localization outside the nuclear meta compartment is mitochondria.
Figure 1. Examples of proteins localized to the nucleoli. UTP6 is suggested to be involved in processing of pre rRNA (detected in A-431 cells). RPF1 is a protein believed to be required for ribosome biogenesis (detected in SK-MEL-30 cells). NIFK is known to localize to the nucleoli, but its function is still unclear (detected in A-431 cells).
7% (1410 proteins) of all human proteins have been experimentally detected in the nucleoli by the Human Protein Atlas.
436 proteins in the nucleoli are supported by experimental evidence and out of these 120 proteins are enhanced by the Human Protein Atlas.
1245 proteins in the nucleoli have multiple locations.
358 proteins in the nucleoli show a cell to cell variation. Of these 316 show a variation in intensity and 56 a spatial variation.
Nucleolar proteins are mainly involved in rRNA processing.
Figure 2. 7% of all human protein-coding genes encode proteins localized to the nucleoli. Each bar is clickable and gives a search result of genes encoding proteins that belong to the selected category.
The nucleoli are non-membrane enclosed, highly conserved, sub-organelles within the nucleus. They are formed around nucleolus organizer regions (NORs) consisting of ribosomal DNA (rDNA) and are structurally organized into three different sub regions; the fibrillar center (FC), the dense fibrillar component (DFC) and the granular component (GC) (Boisvert FM et al. (2007); Scheer U et al. (1999)). A selection of proteins localized to the nucleoli that are suitable as nucleoli markers can be found in Table 1.
Table 1. Selection of proteins suitable as markers for the nucleoli or its substructures.
A majority of the nucleolar proteins show staining throughout the whole nucleolar area, while roughly 20% display a more refined staining pattern. The staining of fibrillar centers and/or dense fibrillar component appears as clusters of spots for most cell lines while for others, for example MCF-7 and U-251, only one larger spot is seen. Some proteins localize to the rim of the nucleolus, which is visible as a thin circle around the nucleolus, which could be associated to either the GC or the perinucleolar heterochromatin surrounding the nucleolus (Németh A et al. (2011)). A recent study suggests that the protein MKI67, which is localized to the nucleoli rim, functions like a surfactant to create non-membranous barriers in the cell. Therefore, proteins with similar staining patterns could have a similar function (Cuylen S et al. (2016); Stenström L et al. (2020)). MKI67 and other immunofluorescent images of different nucleolar substructures can be seen in Figure 3. Upon entry into mitosis, rRNA transcription and RNP processing shuts down and the nucleoli are disassembled. In telophase and early G1, the nucleolar organization is re-established.
Figure 3. Examples of the morphology of the nucleoli in different cell lines as well as the nucleolar substructures and staining patterns. Immunofluorescent staining of KRI1 in HEK 239, MCF-7 and U-2 OS cells. NOLC1 might play a role in maintaining the structure of the fibrillar center and the dense fibrillar component in the nucleoli, an is localized to the fibrillar center (detected in HEK293 cells). UBTF is involved in the activation of RNA polymerase I and is localized to the fibrillar center (detected in U-2 OS cells). MKI67 has been found to maintain mitotic chromosome integrity and is a well-known cellular proliferation marker (detected in U-251 MG cells).
Figure 4. 3D-view of nucleoli in U-2 OS cells, visualized by immunofluorescent staining of NOP56. The morphology of nucleoli in human induced stem cells can be seen in the Allen Cell Explorer.
The function of nucleoli
The nucleolus is responsible for the synthesis, processing and assembly of ribosomes, a complex process controlled in the nucleolar sub regions (Boisvert FM et al. (2007); Scheer U et al. (1999); Németh A et al. (2011)). The border between the FC and the DFC contains proteins from the RNA polymerase I complex and is the region where pre-ribosomal RNA (pre-rRNA) is transcribed from rDNA. The pre-rRNA is later modified by proteins in the DFC followed by assembly of the ribosome subunits in the GC (Scheer U et al. (1999)). As is the case for the majority of organelles, the proteome of the nucleolus is dynamic and has been shown to consist of multiple overlapping sets of proteins that are interchanging dependent on the cell state. The need for translational capacity varies with different cell cycle phases, and transcriptional capacity is heavily dependent on the amount of ribosomes available. In addition to being responsible for ribosome assembly, the nucleolus has also been found to comprise of proteins involved in cell cycle regulation and cellular stress responses (Boisvert FM et al. (2007); Visintin R et al. (2000)).
Several genetic disorders such as Werner syndrome, Fragile X syndrome and Treacher Collins syndrome have been linked to nucleolar proteins (Marciniak RA et al. (1998); Tamanini F et al. (2000); Willemsen R et al. (1996); Isaac C et al. (2000)). Moreover, the nucleolar size increases with the proliferative ability of cells, suggesting that the nucleoli play an important role in development of cancer and could therefore be a potential target for cancer therapy (Drygin D et al. (2010)).
Gene Ontology (GO) analysis of the proteins mainly localized to the nucleoli reveal functions that are well in-line with already known functions for the compartment. The enriched terms for the GO domain Biological Process are related to ribosome biogenesis, but also regulation of gene expression, chromosome organization and signal transduction (Figure 5a), while enrichment analysis of the GO domain Molecular Function gives enrichment for RNA polymerase I activity, as well RNA binding and processing activities (Figure 5b). A list of highly expressed nucleolar proteins are summarized in Table 2.
Figure 5a. Gene Ontology-based enrichment analysis for the nucleolar 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 nucleolar 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 localized nucleolar proteins across different cell lines.
Of the nucleolar proteins identified in the Subcellular Section, approximately 88% (n=1245) also localize to other cell compartments (Figure 6). 35% (n=489) of the nucleolar proteins only localize to other nuclear structures. The network plot shows that the most common locations shared with nucleoli are nucleoplasm, cytosol and mitochondria. Given that the nucleoli are responsible for synthesis and assembly of ribosomes that later are exported to the cytoplasm, many of the proteins localized to both the nucleoli and the cytoplasmic structures are most likely involved in ribosome biogenesis, transport and function. Nucleolar protein that additionally localize to the nucleoplasm and mitochondria, respectively, are significantly overrepresented, while nucleolar proteins that additionally localize to vesicles, the Golgi apparatus, the cytosol and centrosomes, respectively, are significantly underrepresented. Examples of multilocalizing proteins within the nucleolar proteome can be seen in Figure 7.
Figure 6. Interactive network plot of nucleolar proteins with multiple localizations. The numbers in the connecting nodes show the proteins that are localized to the nucleoli and to one or more additional locations. Only connecting nodes containing more than one protein and at least 0.5% of proteins in the nucleolar 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 7. Examples of multilocalizing proteins in the nucleolar proteome. The examples show common or overrepresented combinations for multilocalizing proteins in the nucleolar proteome. EXOSC10 is known to be involved in multiple RNA processing pathways in the nucleolus, nucleus and the cytoplasm (detected in U-2 OS cells). APTX is known to be involved in DNA repair and is localized to the nucleoplasm and the nucleoli (detected in PC-3 cells). SPATS2L is known to localize to the nucleoli and within cytoplasmic stress granules during oxidative stress but its function is still unknown (detected in U-2 OS cells).
Expression levels of nucleoli proteins in tissue
Transcriptome analysis and classification of genes into tissue distribution categories (Figure 8) shows that genes encoding proteins that localize to nucleoli are more likely to either be detected in a single tissue or detected in all tissues, compared to all genes presented in the Subcellular Section. Significantly lower portions of nucleoli-associated genes are detected in some or many of the tissues. Thus, these genes tend to either be ubiquitously expressed, or show a strict tissue-specific expression.
Figure 8. Bar plot showing the percentage of genes in different tissue distribution categories for nucleoli-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
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
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
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
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
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
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
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
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
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
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
Becht E et al., Dimensionality reduction for visualizing single-cell data using UMAP.Nat Biotechnol. (2018)
PubMed: 30531897 DOI: 10.1038/nbt.4314
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
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
Leduc C et al., Intermediate filaments in cell migration and invasion: the unusual suspects.Curr Opin Cell Biol. (2015)
PubMed: 25660489 DOI: 10.1016/j.ceb.2015.01.005
Lowery J et al., Intermediate Filaments Play a Pivotal Role in Regulating Cell Architecture and Function.J Biol Chem. (2015)
PubMed: 25957409 DOI: 10.1074/jbc.R115.640359
Robert A et al., Intermediate filament dynamics: What we can see now and why it matters.Bioessays. (2016)
PubMed: 26763143 DOI: 10.1002/bies.201500142
Janmey PA et al., Viscoelastic properties of vimentin compared with other filamentous biopolymer networks.J Cell Biol. (1991)
PubMed: 2007620
Köster S et al., Intermediate filament mechanics in vitro and in the cell: from coiled coils to filaments, fibers and networks.Curr Opin Cell Biol. (2015)
PubMed: 25621895 DOI: 10.1016/j.ceb.2015.01.001
Herrmann H et al., Intermediate filaments: from cell architecture to nanomechanics.Nat Rev Mol Cell Biol. (2007)
PubMed: 17551517 DOI: 10.1038/nrm2197
Gauster M et al., Keratins in the human trophoblast.Histol Histopathol. (2013)
PubMed: 23450430 DOI: 10.14670/HH-28.817
Ouyang W et al., Analysis of the Human Protein Atlas Image Classification competition.Nat Methods. (2019)
PubMed: 31780840 DOI: 10.1038/s41592-019-0658-6
Janke C., The tubulin code: molecular components, readout mechanisms, and functions.J Cell Biol. (2014)
PubMed: 25135932 DOI: 10.1083/jcb.201406055
Goodson HV et al., Microtubules and Microtubule-Associated Proteins.Cold Spring Harb Perspect Biol. (2018)
PubMed: 29858272 DOI: 10.1101/cshperspect.a022608
Conde C et al., Microtubule assembly, organization and dynamics in axons and dendrites.Nat Rev Neurosci. (2009)
PubMed: 19377501 DOI: 10.1038/nrn2631
Wloga D et al., Post-translational modifications of microtubules.J Cell Sci. (2010)
PubMed: 20930140 DOI: 10.1242/jcs.063727
Schmoranzer J et al., Role of microtubules in fusion of post-Golgi vesicles to the plasma membrane.Mol Biol Cell. (2003)
PubMed: 12686609 DOI: 10.1091/mbc.E02-08-0500
Skop AR et al., Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms.Science. (2004)
PubMed: 15166316 DOI: 10.1126/science.1097931
Schaefer AM et al., The epidemiology of mitochondrial disorders--past, present and future.Biochim Biophys Acta. (2004)
PubMed: 15576042 DOI: 10.1016/j.bbabio.2004.09.005
Lange A et al., Classical nuclear localization signals: definition, function, and interaction with importin alpha.J Biol Chem. (2007)
PubMed: 17170104 DOI: 10.1074/jbc.R600026200
Ashmarina LI et al., 3-Hydroxy-3-methylglutaryl coenzyme A lyase: targeting and processing in peroxisomes and mitochondria.J Lipid Res. (1999)
PubMed: 9869651
Wang SC et al., Nuclear translocation of the epidermal growth factor receptor family membrane tyrosine kinase receptors.Clin Cancer Res. (2009)
PubMed: 19861462 DOI: 10.1158/1078-0432.CCR-08-2813
Pancholi V., Multifunctional alpha-enolase: its role in diseases.Cell Mol Life Sci. (2001)
PubMed: 11497239 DOI: 10.1007/pl00000910
Chapple CE et al., Extreme multifunctional proteins identified from a human protein interaction network.Nat Commun. (2015)
PubMed: 26054620 DOI: 10.1038/ncomms8412
Dechat T et al., Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin.Genes Dev. (2008)
PubMed: 18381888 DOI: 10.1101/gad.1652708
Gruenbaum Y et al., The nuclear lamina comes of age.Nat Rev Mol Cell Biol. (2005)
PubMed: 15688064 DOI: 10.1038/nrm1550
Stuurman N et al., Nuclear lamins: their structure, assembly, and interactions.J Struct Biol. (1998)
PubMed: 9724605 DOI: 10.1006/jsbi.1998.3987
Paine PL et al., Nuclear envelope permeability.Nature. (1975)
PubMed: 1117994
Reichelt R et al., Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components.J Cell Biol. (1990)
PubMed: 2324201
CALLAN HG et al., Experimental studies on amphibian oocyte nuclei. I. Investigation of the structure of the nuclear membrane by means of the electron microscope.Proc R Soc Lond B Biol Sci. (1950)
PubMed: 14786306
WATSON ML., The nuclear envelope; its structure and relation to cytoplasmic membranes.J Biophys Biochem Cytol. (1955)
PubMed: 13242591
BAHR GF et al., The fine structure of the nuclear membrane in the larval salivary gland and midgut of Chironomus.Exp Cell Res. (1954)
PubMed: 13173504
Terasaki M et al., A new model for nuclear envelope breakdown.Mol Biol Cell. (2001)
PubMed: 11179431
Dultz E et al., Systematic kinetic analysis of mitotic dis- and reassembly of the nuclear pore in living cells.J Cell Biol. (2008)
PubMed: 18316408 DOI: 10.1083/jcb.200707026
Salina D et al., Cytoplasmic dynein as a facilitator of nuclear envelope breakdown.Cell. (2002)
PubMed: 11792324
Beaudouin J et al., Nuclear envelope breakdown proceeds by microtubule-induced tearing of the lamina.Cell. (2002)
PubMed: 11792323
Gerace L et al., The nuclear envelope lamina is reversibly depolymerized during mitosis.Cell. (1980)
PubMed: 7357605
Ellenberg J et al., Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis.J Cell Biol. (1997)
PubMed: 9298976
Yang L et al., Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis.J Cell Biol. (1997)
PubMed: 9182656
Bione S et al., Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy.Nat Genet. (1994)
PubMed: 7894480 DOI: 10.1038/ng1294-323
Boisvert FM et al., The multifunctional nucleolus.Nat Rev Mol Cell Biol. (2007)
PubMed: 17519961 DOI: 10.1038/nrm2184
Cuylen S et al., Ki-67 acts as a biological surfactant to disperse mitotic chromosomes.Nature. (2016)
PubMed: 27362226 DOI: 10.1038/nature18610
Stenström L et al., Mapping the nucleolar proteome reveals a spatiotemporal organization related to intrinsic protein disorder.Mol Syst Biol. (2020)
PubMed: 32744794 DOI: 10.15252/msb.20209469
Visintin R et al., The nucleolus: the magician's hat for cell cycle tricks.Curr Opin Cell Biol. (2000)
PubMed: 10801456
Marciniak RA et al., Nucleolar localization of the Werner syndrome protein in human cells.Proc Natl Acad Sci U S A. (1998)
PubMed: 9618508
Tamanini F et al., The fragile X-related proteins FXR1P and FXR2P contain a functional nucleolar-targeting signal equivalent to the HIV-1 regulatory proteins.Hum Mol Genet. (2000)
PubMed: 10888599
Willemsen R et al., Association of FMRP with ribosomal precursor particles in the nucleolus.Biochem Biophys Res Commun. (1996)
PubMed: 8769090 DOI: 10.1006/bbrc.1996.1126
Isaac C et al., Characterization of the nucleolar gene product, treacle, in Treacher Collins syndrome.Mol Biol Cell. (2000)
PubMed: 10982400
Drygin D et al., The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer.Annu Rev Pharmacol Toxicol. (2010)
PubMed: 20055700 DOI: 10.1146/annurev.pharmtox.010909.105844
MENU
The Human Protein Atlas project is funded
