GO:0005737 cytoplasm: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005737 (cytoplasm) is defined by QuickGO as the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
• The cytoplasm is not a passive space: it is an active compartment that mediates inheritance, apoptotic cell death, mRNA quality control, and metabolic compartmentalization.
• Cytoplasmic composition and volume are tightly regulated and can be experimentally segmented and quantified in imaging workflows.
• Compartment-specific biochemistry, such as the distinct behavior of GAPDH in the cytoplasm versus the nucleus, demonstrates that the cytoplasm has its own catalytic environment.
• Cytoplasmic decay of defective mRNA is mechanistically linked to transcriptional adaptation, connecting cytoplasmic RNA surveillance to nuclear gene expression.
• Cytoplasmic effects are measurable at the organismal level, including in hybrid crop traits such as rancidity-related phenotypes in pearl millet.
Description
GO:0005737 (cytoplasm) is a cellular_component term in the Gene Ontology describing the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. In practice, the cytoplasm is the aqueous and organelle-containing interior of the cell where many biosynthetic, degradative, and signaling reactions occur, and it is functionally distinct from the nucleus and the plasma membrane. Because the cytoplasm is the site of translation, intermediary metabolism, and many quality-control pathways, its composition and dynamics are central to cell biology. The cytoplasm is also a carrier of inherited information and a mediator of cell-fate decisions, as shown by studies of cytoplasmic inheritance and cytoplasm-mediated apoptotic cell death in mouse zygotes. For researchers, the cytoplasm is both a physical compartment to be imaged and segmented and a biochemical environment whose activities differ from those of the nucleus. Understanding the cytoplasm therefore requires integrating cell biology, imaging, and molecular genetics approaches.
cytoplasm At A Glance
| GO ID | GO:0005737 |
|---|---|
| GO term | cytoplasm |
| Ontology | cellular_component |
| Synonym | None listed in QuickGO |
| Definition | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| Major function | Houses translation, metabolism, quality control, and signaling reactions outside the nucleus and plasma membrane. |
| Compartmental relationships | Excludes the plasma membrane and nucleus; includes other subcellular structures. |
| Experimental relevance | Can be segmented and quantified in imaging workflows and studied biochemically as a distinct compartment. |
| Representative biology | Cytoplasmic inheritance, apoptotic cell death, mRNA decay, and compartment-specific enzyme behavior. |
What Is GO:0005737?
According to the QuickGO definition, GO:0005737 (cytoplasm) refers to the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. This means the term captures the material inside the cell boundary but outside the nuclear envelope, encompassing the cytosol and the various membrane-bound and non-membrane-bound structures suspended within it. It is a cellular_component term, so it is used to annotate where gene products localize or where processes occur, rather than to describe a molecular activity or a biological program. The definition explicitly excludes the plasma membrane and the nucleus, which distinguishes cytoplasm from terms such as nucleus or plasma membrane. Because the definition includes other subcellular structures, cytoplasmic annotations can overlap with organelle annotations when a protein or process is associated with structures embedded in the cytoplasm.
Why Is cytoplasm Important in Cell Biology?
The cytoplasm is important because it is the compartment where many essential cellular processes occur and where defects can directly influence cell fate and organismal phenotypes. Studies in mouse zygotes show that the cytoplasm mediates both developmental and oxidation-induced apoptotic cell death, indicating that cytoplasmic factors can determine whether a cell survives or dies. Cytoplasmic inheritance provides a mechanism by which traits are transmitted through the cytoplasm rather than the nucleus, with broad implications for genetics and evolution. In addition, the cytoplasm is a site of mRNA quality control: cytoplasmic decay of translation-defective mRNA is mechanistically linked to transcriptional adaptation, connecting cytoplasmic surveillance to nuclear transcriptional responses. Compartment-specific biochemistry further shows that the same enzyme can behave differently in the cytoplasm versus the nucleus, underscoring that the cytoplasm is a distinct regulatory environment. Finally, cytoplasmic effects can be measured in applied contexts such as crop hybrids, where cytoplasm influences rancidity-related traits.
• The cytoplasm mediates apoptotic cell death in mouse zygotes, linking cytoplasmic factors to developmental outcomes.
• Cytoplasmic inheritance allows traits to be transmitted through the cytoplasm, with implications for genetics and evolution.
• Cytoplasmic decay of translation-defective mRNA is mechanistically linked to transcriptional adaptation.
• Compartment-specific enzyme behavior, such as GAPDH activity differences between cytoplasm and nucleus, shows the cytoplasm is biochemically distinct.
• Cytoplasm effects can influence agricultural traits such as rancidity-related phenotypes in pearl millet hybrids.
• The cytoplasm can be segmented and quantified in imaging studies, supporting quantitative cell biology.
• Nucleoporin complexes such as Nup214-Nup88 are required for CRM1-mediated 60S preribosomal nuclear export, illustrating how nuclear and cytoplasmic compartments communicate.
• Naturally minimized eukaryotic cytoplasm in the periplastidal compartment provides a model for understanding minimal cytoplasmic functions.
What Happens During cytoplasm?
Cytoplasmic inheritance and transmission
In simple terms: Some traits are passed down through the cytoplasm rather than through the nucleus.
Cytoplasmic inheritance describes the transmission of genetic or epigenetic information through cytoplasmic components rather than through nuclear chromosomes. This mode of inheritance means that cytoplasmic factors can carry information across generations and influence phenotypes independently of nuclear genes. In experimental and evolutionary contexts, cytoplasmic inheritance is studied to understand how non-nuclear information contributes to trait variation and adaptation. Because the cytoplasm is defined as the contents of a cell excluding the plasma membrane and nucleus, cytoplasmic inheritance is conceptually distinct from nuclear inheritance and is often analyzed using cytoplasmic replacement or cytoplasmic effect designs.
Cytoplasm-mediated apoptotic cell death
In simple terms: The cytoplasm can send signals that cause a cell to self-destruct.
In mouse zygotes, the cytoplasm mediates both development and oxidation-induced apoptotic cell death, demonstrating that cytoplasmic factors can actively promote cell death pathways. This means that the cytoplasmic environment is not merely a passive backdrop but can determine whether a cell undergoes apoptosis in response to developmental cues or oxidative stress. Such findings are relevant to understanding early embryonic development and the cellular response to oxidative damage. The cytoplasm therefore functions as a signaling and execution compartment for cell death decisions.
Cytoplasmic mRNA decay and transcriptional adaptation
In simple terms: When mRNA is defective, the cytoplasm can degrade it and this can trigger changes in gene transcription.
Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation have been described, showing that cytoplasmic RNA surveillance can be coupled to nuclear transcriptional responses. In this process, translation-defective mRNA is degraded in the cytoplasm, and this decay is mechanistically linked to adaptation at the transcriptional level. This connection highlights the cytoplasm as a quality-control compartment whose activities can feed back to the nucleus. The finding is important for understanding how cells respond to defective gene expression and how cytoplasmic and nuclear processes are coordinated.
Compartment-specific biochemistry in the cytoplasm
In simple terms: The same enzyme can behave differently depending on whether it is in the cytoplasm or the nucleus.
Biochemical evidence shows that the whole compartment activity behavior of GAPDH differs between the cytoplasm and the nucleus, indicating that the cytoplasm provides a distinct catalytic environment. This compartment-specific behavior means that measurements of enzyme activity must consider subcellular localization, because the same protein can have different effective activities in different compartments. Such findings support the view that the cytoplasm is not simply a diluted version of the nucleus but a biochemically distinct compartment. This has implications for interpreting metabolic and signaling data in cell biology.
Cytoplasmic communication with the nucleus
In simple terms: The cytoplasm and nucleus exchange materials through nuclear pores.
The Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60S preribosomal nuclear export, illustrating that cytoplasmic and nuclear compartments are connected by specific transport machinery. This transport function is essential for delivering preribosomal subunits from the nucleus to the cytoplasm, where they participate in ribosome assembly and translation. The requirement for specific nucleoporins shows that the boundary between nucleus and cytoplasm is actively regulated. Consequently, the cytoplasm depends on nuclear export pathways to receive key components.
Minimal cytoplasmic systems
In simple terms: Some organisms have a very simplified cytoplasm that can be studied as a minimal system.
The periplastidal compartment has been described as a naturally minimized eukaryotic cytoplasm, providing a model for understanding the minimal functions of a cytoplasm-like compartment. Studying such minimized systems can reveal which cytoplasmic functions are essential and which are dispensable. This comparative perspective helps researchers interpret cytoplasmic organization across diverse eukaryotes. It also underscores that the cytoplasm is a definable compartment whose complexity can vary.
Key Genes Involved in GO:0005737 cytoplasm
The following genes and proteins are experimentally linked to cytoplasmic functions, including cytoplasmic inheritance, mRNA decay, apoptotic cell death, nuclear export, and compartment-specific biochemistry.
| Gene | Major Role | Research Relevance |
|---|---|---|
| GAPDH | Glycolytic enzyme with compartment-specific activity behavior | Used to study biochemical differences between cytoplasm and nucleus |
| NUP214 | Nucleoporin component of the Nup214-Nup88 subcomplex | Required for CRM1-mediated 60S preribosomal nuclear export, linking nucleus and cytoplasm |
| NUP88 | Nucleoporin component of the Nup214-Nup88 subcomplex | Required for CRM1-mediated 60S preribosomal nuclear export |
| CRM1 | Nuclear export receptor | Mediates 60S preribosomal export dependent on Nup214-Nup88 |
| Not specified in cited literature | Cytoplasmic inheritance factors | Studied in the context of inheritance through the cytoplasm |
| Not specified in cited literature | Cytoplasmic mediators of apoptosis | Studied in mouse zygotes for development and oxidation-induced cell death |
| Not specified in cited literature | Cytoplasmic mRNA decay machinery | Linked to transcriptional adaptation for translation-defective mRNA |
| Not specified in cited literature | Periplastidal compartment components | Model for a naturally minimized eukaryotic cytoplasm |
| Not specified in cited literature | Cytoplasmic effectors of rancidity traits | Studied in pearl millet hybrids for cytoplasm effects |
| Not specified in cited literature | Nucleus and cytoplasm segmentation markers | Used in imaging to distinguish compartments |
How Is cytoplasm Regulated?
Cytoplasmic processes are regulated at multiple levels, including through nuclear export machinery that controls which components enter the cytoplasm. The Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60S preribosomal nuclear export, meaning that the composition of the cytoplasm is actively regulated by nuclear export pathways. Cytoplasmic mRNA decay is also regulated and can be mechanistically linked to transcriptional adaptation, providing a feedback route from the cytoplasm to the nucleus. In addition, cytoplasmic inheritance implies that cytoplasmic factors can be transmitted and regulated independently of nuclear genes. Compartment-specific enzyme behavior, such as that of GAPDH, further indicates that cytoplasmic activities are regulated by the local environment rather than solely by protein abundance.
cytoplasm and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Not specified in cited literature | Apoptotic cell death and oxidative stress in early development | Mouse zygote models for cytoplasm-mediated apoptosis |
| Not specified in cited literature | Transcriptional adaptation linked to cytoplasmic mRNA decay | Cell models with translation-defective mRNA reporters |
| NUP214 | Nuclear export defects affecting 60S preribosomal export | Knockout or knockdown of NUP214 to assess CRM1-mediated export |
| NUP88 | Nuclear export defects affecting 60S preribosomal export | Knockout or knockdown of NUP88 to assess CRM1-mediated export |
| GAPDH | Compartment-specific metabolism | Compartment-resolved activity assays in cytoplasm and nucleus |
Cytoplasmic dysfunction and cell death
The cytoplasm mediates both development and oxidation-induced apoptotic cell death in mouse zygotes, indicating that cytoplasmic dysfunction can directly influence cell survival and death decisions. This has implications for understanding diseases in which inappropriate apoptosis or oxidative stress contributes to pathology. Because the cytoplasm is the site of many stress-responsive pathways, defects in cytoplasmic regulation can alter cell fate.
Cytoplasmic mRNA decay and gene expression disease mechanisms
Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation suggest that defects in cytoplasmic RNA surveillance can affect transcriptional programs. When translation-defective mRNA is not properly handled in the cytoplasm, the resulting transcriptional adaptation may contribute to altered gene expression states relevant to disease. This connection places cytoplasmic quality control in the broader context of gene regulation and disease mechanisms.
Nuclear-cytoplasmic transport and ribosome-related disease
The Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60S preribosomal nuclear export, so defects in this transport step can impair cytoplasmic delivery of ribosomal subunits. Impaired nuclear export can affect ribosome assembly and translation in the cytoplasm, which is relevant to ribosomopathies and other diseases linked to defective ribosome biogenesis. This illustrates how cytoplasmic composition depends on nuclear export and how transport defects can have downstream cellular consequences.
Compartment-specific metabolism and disease
Biochemical evidence that GAPDH whole compartment activity behavior differs between the cytoplasm and nucleus suggests that compartment-specific metabolic changes can be relevant to disease. Because GAPDH participates in glycolysis and other cellular functions, altered compartmentalization could affect metabolic and signaling pathways. Studying such compartment-specific behavior may help interpret metabolic phenotypes in disease research.
From cytoplasm-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does a candidate gene regulate cytoplasmic mRNA decay and transcriptional adaptation? | Knockout cell model with translation-defective mRNA reporters |
| Is a nucleoporin required for CRM1-mediated 60S preribosomal nuclear export? | Knockout or point-mutation models of NUP214 and NUP88 |
| Does a cytoplasmic factor mediate apoptotic cell death? | Mouse zygote or early embryo models with cytoplasmic manipulation |
| Can cytoplasmic inheritance be tracked experimentally? | Cytoplasmic replacement or hybridization designs |
| Can cytoplasm and nucleus be quantitatively segmented? | Imaging-based segmentation workflows |
| Does an enzyme behave differently in cytoplasm versus nucleus? | Compartment-resolved biochemical assays for GAPDH |
How to Study the cytoplasm Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Nucleus and cytoplasm segmentation | Compartment boundaries and signal distribution | Quantifying cytoplasmic versus nuclear markers in images |
| Compartment-resolved enzyme activity assay | Activity of an enzyme in cytoplasm versus nucleus | Studying GAPDH compartment-specific behavior |
| Translation-defective mRNA reporter assay | Cytoplasmic mRNA decay and transcriptional adaptation | Dissecting mRNA quality control feedback |
| Nuclear export assay for 60S subunits | CRM1-mediated 60S preribosomal export | Testing Nup214-Nup88 requirements |
| Cytoplasmic inheritance analysis | Transmission of traits through cytoplasm | Studying non-nuclear inheritance |
| Cytoplasm-mediated apoptosis assay | Cell death induced by cytoplasmic factors | Mouse zygote studies of oxidative stress |
| Cytoplasm effect trait analysis | Phenotypes associated with cytoplasmic background | Crop hybrid trait evaluation |
| Minimal cytoplasm comparative analysis | Functions retained in a minimized cytoplasm | Studying periplastidal compartment biology |
Imaging and compartment segmentation
Threshold estimation based on local minima has been developed for nucleus and cytoplasm segmentation, enabling quantitative separation of these compartments in microscopy images. Such methods allow researchers to measure cytoplasmic area, intensity, and localization of markers in a reproducible way. Segmentation is particularly useful when comparing cytoplasmic versus nuclear signals for the same protein or reporter. These imaging approaches complement biochemical fractionation by providing spatial information.
Biochemical compartment analysis
Biochemical evidence that GAPDH whole compartment activity behavior differs between the cytoplasm and nucleus demonstrates the value of compartment-resolved activity assays. Such assays can reveal whether an enzyme's effective activity depends on its subcellular location. This approach is useful for interpreting metabolic data and for testing whether a protein functions differently in the cytoplasm versus the nucleus. Compartment-resolved biochemistry can also validate imaging-based observations.
RNA surveillance and transcriptional adaptation assays
Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation can be studied using reporter mRNAs and transcriptional readouts. These assays measure both the degradation of defective mRNA in the cytoplasm and the resulting changes in transcription. They are useful for dissecting how cytoplasmic quality control feeds back to nuclear gene expression. Such experiments help define the molecular steps connecting cytoplasmic decay to transcriptional adaptation.
Nuclear export and transport assays
The requirement of the Nup214-Nup88 nucleoporin subcomplex for CRM1-mediated 60S preribosomal nuclear export can be studied by perturbing these components and monitoring preribosomal subunit localization. Transport assays can determine whether 60S subunits reach the cytoplasm and whether export is impaired. These experiments link nuclear export machinery to cytoplasmic composition. They are relevant for understanding how the cytoplasm receives ribosomal components.
How CRISPR Can Be Used to Study GO:0005737 cytoplasm
Knockout
CRISPR knockout can be used to remove genes whose products act in the cytoplasm or control cytoplasmic composition, such as NUP214 or NUP88, to test whether CRM1-mediated 60S preribosomal nuclear export is impaired. Knockout of cytoplasmic quality-control factors can also be used to test the link between cytoplasmic mRNA decay and transcriptional adaptation. In crop or organismal studies, knockout can help determine whether cytoplasmic effects on traits such as rancidity-related phenotypes depend on specific nuclear genes. Knockout models are therefore a direct way to test causality for cytoplasm-associated functions.
Point Mutation
Point mutation can be used to dissect specific residues required for cytoplasmic functions, such as domains of nucleoporins needed for CRM1-mediated 60S preribosomal export. Point mutations can also be introduced into enzymes like GAPDH to test whether compartment-specific activity behavior depends on particular residues. In mRNA quality-control studies, point mutations in reporter mRNAs can be used to trigger translation defects and monitor cytoplasmic decay and transcriptional adaptation. This approach allows fine-grained structure-function analysis within the cytoplasmic environment.
Knock-in
Knock-in of tags or reporters can be used to visualize cytoplasmic proteins and track their localization relative to the nucleus and plasma membrane. Tagged knock-in of nucleoporins or export factors can help monitor nuclear export events that deliver components to the cytoplasm. Knock-in of reporter constructs can also be used to study cytoplasmic mRNA decay and the resulting transcriptional adaptation. These models support live-cell and fixed-cell imaging of cytoplasmic dynamics.
Overexpression
Overexpression can be used to test whether increasing the level of a cytoplasmic factor is sufficient to alter cell fate, such as promoting or preventing apoptosis in early embryos. Overexpression of export-related proteins can also be used to test whether nuclear export capacity limits cytoplasmic delivery of ribosomal subunits. In biochemical studies, overexpression of enzymes like GAPDH can be combined with compartment-resolved assays to test whether activity behavior changes with abundance. Overexpression models are therefore useful for gain-of-function tests of cytoplasmic processes.
How EDITGENE Supports cytoplasm Research
Researchers studying cytoplasm-related genes often need to determine whether a candidate gene is causally involved in cytoplasmic functions such as mRNA decay, nuclear export, apoptotic signaling, or compartment-specific metabolism. Establishing causality typically requires loss-of-function and gain-of-function experiments in relevant cell models, together with readouts that resolve cytoplasmic versus nuclear events. EDITGENE provides CRISPR-based cell model services that support these experimental needs, from knockout to knock-in and overexpression, as well as library screening and bioinformatics.
Contact EDITGENE today to design your custom CRISPR model for cytoplasm research.
Frequently Asked Questions About cytoplasm
What is GO:0005737?
GO:0005737 is the Gene Ontology cellular_component term for cytoplasm, defined as the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
What is the cytoplasm?
The cytoplasm is the material inside a cell but outside the nucleus and plasma membrane, and it includes other subcellular structures; it is the compartment where many biosynthetic and quality-control reactions occur.
What genes are involved in cytoplasm-related functions?
Genes and proteins linked to cytoplasmic functions include GAPDH, NUP214, NUP88, and CRM1, which are involved in compartment-specific biochemistry and nuclear export to the cytoplasm.
How is the cytoplasm studied experimentally?
The cytoplasm can be studied using imaging-based segmentation, compartment-resolved biochemical assays, mRNA decay assays, and nuclear export assays.
Does the cytoplasm mediate apoptosis?
Yes, studies in mouse zygotes show that the cytoplasm mediates both development and oxidation-induced apoptotic cell death.
What is cytoplasmic inheritance?
Cytoplasmic inheritance is the transmission of traits through cytoplasmic components rather than nuclear chromosomes.
How does cytoplasmic mRNA decay relate to transcription?
Cytoplasmic decay of translation-defective mRNA is mechanistically linked to transcriptional adaptation, connecting cytoplasmic quality control to nuclear gene expression.
What is the role of Nup214-Nup88 in the cytoplasm?
The Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60S preribosomal nuclear export, which delivers ribosomal subunits to the cytoplasm.
Can the cytoplasm be segmented in images?
Yes, threshold estimation based on local minima has been developed for nucleus and cytoplasm segmentation in imaging workflows.
Why does the cytoplasm matter for disease research?
Cytoplasmic processes such as apoptosis, mRNA decay, and nuclear export can influence cell fate and gene expression, making them relevant to disease mechanisms.
Conclusion
GO:0005737 (cytoplasm) is a fundamental cellular_component term describing the contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. Research across genetics, cell biology, and biochemistry shows that the cytoplasm is an active compartment involved in inheritance, apoptotic cell death, mRNA quality control, nuclear export, and compartment-specific metabolism. Because cytoplasmic functions can influence cell fate and gene expression, they are relevant to both basic biology and disease research. Experimental approaches ranging from imaging segmentation to compartment-resolved biochemistry and CRISPR models provide complementary ways to study the cytoplasm.
References
- 1. Camus MF et al.. 2022. Inheritance through the cytoplasm.. Heredity (Edinb) 129(1):31-43 PMID: 35525886
- 2. El-Brolosy MA et al.. 2026. Mechanisms linking cytoplasmic decay of translation-defective mRNA to transcriptional adaptation.. Science 391(6786):eaea1272 PMID: 41678638
- 3. Grosche C et al.. 2014. The periplastidal compartment: a naturally minimized eukaryotic cytoplasm.. Curr Opin Microbiol 22:88-93 PMID: 25460801
- 4. Reddy PS et al.. 2025. Cytoplasm effects on rancidity related traits in pearl millet (Pennisetum glaucum (L.) R. Br.) hybrids.. BMC Plant Biol 26(1):85 PMID: 41388361
- 5. Bernad R et al.. 2006. Nup214-Nup88 nucleoporin subcomplex is required for CRM1-mediated 60 S preribosomal nuclear export.. J Biol Chem 281(28):19378-86 PMID: 16675447
- 6. Mayala S et al.. 2022. Threshold estimation based on local minima for nucleus and cytoplasm segmentation.. BMC Med Imaging 22(1):77 PMID: 35473495
- 7. Liu L et al.. 2000. Cytoplasm mediates both development and oxidation-induced apoptotic cell death in mouse zygotes.. Biol Reprod 62(6):1828-34 PMID: 10819789
- 8. Tang HS et al.. 2023. Biochemical evidence that the whole compartment activity behavior of GAPDH differs between the cytoplasm and nucleus.. PLoS One 18(8):e0290892 PMID: 37651389
