GO:0098739 import across plasma membrane: Transport Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0098739 import across plasma membrane describes the directed movement of a substance from outside a cell, across the plasma membrane, and into the cytosol.
• The term covers protein-facilitated transport of small molecules, protein import systems, and specialized uptake routes across the plasma membrane.
• Key protein families include mitochondrial translocases, bacterial outer membrane transporters, and human solute carriers such as choline/ethanolamine transporters.
• Import across the plasma membrane is essential for nutrient acquisition, organelle biogenesis, and cellular homeostasis.
• Dysregulation of import pathways is linked to metabolic disease, cancer, and neurodegeneration.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of import machinery.
Description
GO:0098739 import across plasma membrane is a Gene Ontology biological process term that defines the directed movement of a substance from outside a cell, across the plasma membrane, and into the cytosol. This process is fundamental to how cells acquire nutrients, ions, and macromolecular building blocks, and it encompasses both protein-facilitated transport of small hydrophobic molecules and dedicated protein import systems. The QuickGO definition emphasizes directionality: the substance must cross the plasma membrane and reach the cytosol, distinguishing import from intracellular trafficking or export. Researchers study this term because defects in import across the plasma membrane underlie a wide range of human pathologies, from metabolic disorders to cancer and neurodegeneration. Understanding the molecular players, regulation, and disease relevance of this process is therefore central to cell biology and translational medicine.
import across plasma membrane At A Glance
| GO ID | GO:0098739 |
|---|---|
| GO term | import across plasma membrane |
| Ontology | biological_process |
| Synonym | uptake |
| Definition | The directed movement of some substance from outside of a cell, across the plasma membrane and into the cytosol. |
| Major function | Nutrient acquisition, ion homeostasis, and protein import into cells |
| Related processes | Protein transport, small molecule transport, membrane translocation |
| Cellular context | Plasma membrane and cytosol |
| Representative genes | TOMM20, TOMM40, TIM23, SLC44A1, SLC44A2, TonB, FusB |
What Is GO:0098739?
In our own words, GO:0098739 import across plasma membrane refers to the active or facilitated translocation of a substance from the extracellular space through the plasma membrane and into the cytosol. The process requires a defined directionality (outside to inside) and a final destination in the cytosol, and it can be mediated by membrane-embedded transporters, channels, or protein import machineries.
Why Is import across plasma membrane Important in Cell Biology?
Import across the plasma membrane is a gatekeeping process that determines which substances enter the cell and at what rate, directly influencing metabolism, signaling, and organelle function. Because it controls the cytosolic availability of nutrients and proteins, its dysregulation can drive disease and is a major focus of therapeutic development.
• Controls nutrient uptake and metabolic homeostasis.
• Enables mitochondrial protein import and organelle biogenesis.
• Supports bacterial iron and vitamin acquisition via TonB-dependent transporters.
• Mediates choline and ethanolamine transport in human cells.
• Links to cancer metabolism through altered nutrient import.
• Contributes to neurodegeneration when import pathways fail.
• Provides targets for antimicrobial and anticancer drug discovery.
• Requires precise regulation to avoid toxic accumulation.
• Involves diverse protein families across species.
• Can be studied with CRISPR models for causal gene validation.
What Happens During import across plasma membrane?
Substrate recognition at the cell surface
In simple terms: The cell first identifies what it needs to bring inside.
Import across the plasma membrane begins with substrate recognition by membrane-associated receptors or transporters. For protein import systems, cytosolic or extracellular chaperones deliver substrates to the translocase machinery. In bacterial systems, TonB-dependent transporters bind specific substrates such as iron chelates or vitamins at the outer membrane. In human cells, solute carriers like SLC44A1 and SLC44A2 recognize choline and ethanolamine for uptake. This step ensures selectivity and prevents unwanted molecules from entering the cytosol.
Membrane translocation and channel gating
In simple terms: The substance passes through a protein channel in the membrane.
Once recognized, the substrate is translocated across the lipid bilayer through a proteinaceous channel or transporter. Mitochondrial protein import relies on the TOM complex in the outer membrane and the TIM23 complex in the inner membrane, which together form a continuous import channel. Bacterial outer membrane transporters undergo conformational changes driven by the TonB-ExbB-ExbD complex to move substrates into the periplasm. For small molecules, transporters such as those for choline and ethanolamine undergo alternating access transitions to ferry substrates across the membrane. The FusB protein in some bacteria directly interacts with ferredoxin to energize import.
Energy coupling and driving forces
In simple terms: The cell uses energy to push the substance inward.
Import across the plasma membrane is often energized by ATP hydrolysis, proton motive force, or electrochemical gradients. Mitochondrial protein import uses ATP and the membrane potential across the inner membrane. TonB-dependent transporters harness the proton motive force of the inner membrane to drive substrate uptake across the outer membrane. FusB uses direct interaction with its ferredoxin substrate to energize import. In eukaryotic small molecule transport, ion gradients or ATP hydrolysis power concentrative uptake.
Release into the cytosol and quality control
In simple terms: The substance is delivered to its destination and checked for correctness.
After crossing the membrane, substrates are released into the cytosol or handed off to downstream machinery. Mitochondrial precursor proteins are delivered to the matrix or inner membrane, where they fold or assemble with the help of chaperones. Misfolded or improperly imported proteins are targeted for degradation by quality control systems. For small molecules, cytosolic enzymes may immediately metabolize the imported substrate, maintaining a concentration gradient that favors continued uptake. This final step ensures that import is both efficient and safe for the cell.
Key Genes Involved in GO:0098739 import across plasma membrane
The following genes and proteins are experimentally implicated in import across plasma membrane processes across model organisms.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TOMM20 | Component of the TOM complex for mitochondrial protein import | Core receptor for cytosolic precursor proteins |
| TOMM40 | Channel-forming subunit of the TOM complex | Essential for protein translocation across outer membrane |
| TIMM23 | Subunit of the TIM23 complex | Mediates inner membrane protein import |
| SLC44A1 | Choline transporter | Human choline uptake and phospholipid synthesis |
| SLC44A2 | Choline and ethanolamine transporter | Human choline/ethanolamine transport |
| TonB | Energy transducer for outer membrane transporters | Bacterial iron and vitamin uptake |
| ExbB | Component of TonB-ExbB-ExbD complex | Proton motive force coupling |
| ExbD | Component of TonB-ExbB-ExbD complex | Energy transduction for import |
| FusB | Ferredoxin import energizer | Direct substrate interaction for import |
| FhuA | TonB-dependent transporter | Siderophore uptake in bacteria |
| BtuB | TonB-dependent transporter | Vitamin B12 uptake |
| TOM70 | Mitochondrial import receptor | Recognizes hydrophobic precursor proteins |
| TIM44 | Mitochondrial import motor component | Drives protein translocation into matrix |
| SLC25A | Mitochondrial carrier family | Metabolite import across inner membrane |
| HSP70 | Chaperone for protein import | Facilitates unfolding and translocation |
| YidC | Membrane insertase | Assists protein insertion in bacteria |
| BamA | Outer membrane protein assembly | Folds and inserts outer membrane proteins |
How Is import across plasma membrane Regulated?
Import across the plasma membrane is regulated at multiple levels. In mitochondria, the import of precursor proteins is controlled by cytosolic chaperones, phosphorylation of translocase components, and the availability of ATP and membrane potential. In bacteria, TonB-dependent transport is regulated by iron availability through the Fur repressor and by the energy status of the cell. In human cells, choline and ethanolamine transport is subject to feedback inhibition by downstream metabolites and transcriptional control of SLC44A1 and SLC44A2. Additionally, the FusB system is regulated by the redox state of its ferredoxin substrate. These regulatory layers ensure that import matches cellular demand and prevents toxicity.
import across plasma membrane and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TOMM40 | Neurodegeneration, mitochondrial dysfunction | Knockout and point mutation in neuronal cell lines |
| SLC44A1 | Choline deficiency, neurological disorders | Knockout and overexpression in human cell lines |
| SLC44A2 | Metabolic and neurological phenotypes | Knock-in of patient variants |
| TonB | Bacterial virulence, iron acquisition | Knockout in pathogenic bacteria |
| FusB | Bacterial ferredoxin import | Point mutation and knockout in bacterial models |
Import defects in metabolic and neurological disease
Disruption of import across the plasma membrane can cause metabolic imbalance and neurodegeneration. Mutations in mitochondrial import components such as TOMM40 and TIMM23 are associated with altered mitochondrial function and have been linked to neurodegenerative phenotypes. Defects in choline transport via SLC44A1 and SLC44A2 affect phospholipid metabolism and have been implicated in neurological disorders. In bacteria, loss of TonB-dependent import reduces virulence and survival, making these pathways attractive antimicrobial targets.
Import pathways in cancer
Cancer cells often upregulate nutrient import to support rapid proliferation. Increased expression of solute carriers and mitochondrial protein import machinery supports the metabolic demands of tumor cells. Targeting import pathways, such as choline uptake or mitochondrial translocases, is being explored as a therapeutic strategy. The dependency of cancer cells on specific import routes highlights the importance of understanding GO:0098739 in oncology.
Bacterial import and infectious disease
TonB-dependent transporters are critical for bacterial acquisition of iron and vitamins, which are essential for infection. Pathogens lacking functional TonB or its partners show attenuated virulence. FusB-mediated ferredoxin import in certain bacteria supports metabolic pathways required for survival. These import systems are promising targets for new antibiotics.
From import across plasma membrane-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is TOMM20 required for mitochondrial protein import? | CRISPR knockout in HeLa or HEK293 cells |
| Does a SLC44A1 point mutation alter choline uptake? | Point mutation knock-in in human cell lines |
| Can TonB-dependent transport be monitored in live bacteria? | Tagged knock-in of TonB with fluorescent protein |
| Does overexpression of SLC44A2 increase ethanolamine import? | Overexpression in mammalian cells |
| What is the interactome of FusB during import? | Knock-in of affinity tags followed by proteomics |
| Can import across the plasma membrane be visualized in real time? | Tagged knock-in of transporter with pH-sensitive fluorophore |
How to Study the import across plasma membrane Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro import assay | Protein translocation into mitochondria | Mitochondrial protein import |
| Radiolabeled substrate uptake | Small molecule import rate | Choline/ethanolamine transport |
| Fluorescence microscopy | Real-time import and localization | Live-cell imaging of transporters |
| Affinity purification mass spectrometry | Protein-protein interactions | Import machinery interactome |
| CRISPR knockout screening | Genes required for import | Functional genomics |
| RNA-seq | Transcriptional changes in import genes | Stress response studies |
| Cryo-EM | High-resolution structure of translocases | Mechanistic studies |
| Growth assays on selective media | Bacterial import activity | TonB-dependent transport |
Genetic and biochemical assays for import
Researchers study import across the plasma membrane using genetic knockouts, point mutations, and tagged knock-ins combined with biochemical fractionation. Mitochondrial protein import is often assayed by in vitro import of radiolabeled precursor proteins into isolated mitochondria. Bacterial TonB-dependent transport is measured by growth assays on iron-limited media or by fluorescent substrate uptake. Human choline and ethanolamine transport is quantified using radiolabeled substrates in cell culture.
Imaging and proteomics approaches
Live-cell imaging with fluorescently tagged transporters or substrates allows real-time visualization of import. Super-resolution microscopy can resolve translocase complexes at the plasma membrane. Proteomics, including affinity purification and crosslinking mass spectrometry, identifies interaction partners of import machinery. These methods provide spatial and temporal resolution of import events.
Transcriptomic and functional genomic screens
RNA-seq and ribosome profiling can reveal transcriptional and translational changes in import genes under different conditions. CRISPR library screening enables unbiased identification of genes required for import across the plasma membrane. Such screens have been used to find novel regulators of mitochondrial protein import and small molecule uptake.
Structural and computational methods
Cryo-electron microscopy and X-ray crystallography have resolved structures of TOM, TIM23, and TonB-dependent transporters, revealing mechanisms of substrate translocation. Molecular dynamics simulations complement these structures to model conformational changes during import. Bioinformatics analysis of transporter families helps predict substrate specificity and regulation.
How CRISPR Can Be Used to Study GO:0098739 import across plasma membrane
Knockout
CRISPR knockout of genes such as TOMM20, SLC44A1, or TonB allows researchers to test their requirement for import across the plasma membrane. Knockout cell lines show reduced import activity and downstream phenotypes, providing causal evidence.
Point Mutation
Point mutations can be introduced to mimic patient variants or to disrupt specific residues in transporters. For example, point mutations in SLC44A2 can alter choline binding and transport kinetics. In bacteria, point mutations in TonB can uncouple energy transduction from substrate uptake.
Knock-in
Knock-in of tagged versions of import proteins, such as GFP-TOMM20 or HA-SLC44A1, enables visualization and affinity purification. Tagged knock-ins preserve endogenous regulation and are valuable for studying dynamic import processes.
Overexpression
Overexpression of import machinery or transporters can enhance uptake and reveal rate-limiting steps. For example, overexpression of SLC44A2 increases ethanolamine import and alters phospholipid composition. Overexpression of TonB can boost siderophore uptake in bacteria.
How EDITGENE Supports import across plasma membrane Research
Researchers studying import across plasma membrane-related genes often need to determine whether a candidate gene is causally involved in substrate uptake, which requires precise genetic models. EDITGENE provides end-to-end CRISPR services to generate knockout, point-mutation, knock-in, and overexpression cell models, as well as library screening and bioinformatics support.
Contact EDITGENE today to design your custom CRISPR model for import across plasma membrane research.
Frequently Asked Questions About import across plasma membrane
What is GO:0098739 import across plasma membrane?
GO:0098739 is a Gene Ontology biological process term describing the directed movement of a substance from outside a cell, across the plasma membrane, and into the cytosol.
What genes are involved in import across plasma membrane?
Key genes include TOMM20, TOMM40, TIMM23, SLC44A1, SLC44A2, TonB, ExbB, ExbD, and FusB.
How is import across the plasma membrane regulated?
It is regulated by energy availability, substrate gradients, transcriptional control, and post-translational modifications of transporters.
What diseases are linked to defects in import across the plasma membrane?
Defects are linked to neurodegeneration, metabolic disorders, cancer, and bacterial virulence.
What methods are used to study import across the plasma membrane?
Common methods include in vitro import assays, radiolabeled uptake, fluorescence microscopy, proteomics, and CRISPR screens.
Can CRISPR be used to study import across the plasma membrane?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect import mechanisms.
What is the role of mitochondria in import across the plasma membrane?
Mitochondria rely on protein import across their membranes, which is a specialized form of import across plasma membrane-like processes.
How do bacteria import nutrients across their membranes?
Bacteria use TonB-dependent transporters and other systems to import iron, vitamins, and other substrates.
What is the synonym for GO:0098739?
The synonym is uptake.
Why is import across the plasma membrane important for cancer?
Cancer cells upregulate nutrient import to support growth, making these pathways therapeutic targets.
Conclusion
GO:0098739 import across plasma membrane is a fundamental biological process that governs the entry of substances into the cytosol. Its molecular players range from mitochondrial translocases to bacterial TonB-dependent transporters and human solute carriers, and its dysregulation is linked to diverse diseases. Continued research using CRISPR models and advanced imaging will further illuminate how import is regulated and how it can be targeted therapeutically.
References
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- 2. Guérin J et al.. 2021. Protein import and export across the bacterial outer membrane.. Curr Opin Struct Biol 69:55-62 PMID: 33901701
- 3. Claus S et al.. 2019. Protein-facilitated transport of hydrophobic molecules across the yeast plasma membrane.. FEBS Lett 593(13):1508-1527 PMID: 31166012
- 4. Jain N et al.. 2024. TOM-TIM23 supercomplex formation.. Methods Enzymol 707:3-22 PMID: 39488380
- 5. Wojnowska M et al.. 2020. FusB Energizes Import across the Outer Membrane through Direct Interaction with Its Ferredoxin Substrate.. mBio 11(5) PMID: 33109756
- 6. Ri K et al.. 2024. Molecular mechanism of choline and ethanolamine transport in humans.. Nature 630(8016):501-508 PMID: 38778100
- 7. Braun V. 2024. Substrate Uptake by TonB-Dependent Outer Membrane Transporters.. Mol Microbiol 122(6):929-947 PMID: 39626085
- 8. Hartl FU et al.. 1989. Mitochondrial protein import.. Biochim Biophys Acta 988(1):1-45 PMID: 2642391
