GO:0098712 L-glutamate import across plasma membrane: Transport Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0098712 describes the directed movement of L-glutamate from outside a cell, across the plasma membrane, and into the cytosol.
• The cystine/glutamate antiporter system xc- (SLC7A11/SLC3A2) is a major route for L-glutamate import/export across the plasma membrane in mammalian cells.
• In plants, tonoplast-localized Glu/Asp/GABA exchangers can influence amino acid composition, showing that glutamate transport across membranes is conserved and physiologically important.
• L-glutamate import across the plasma membrane is central to neurotransmitter recycling, metabolic fueling, and redox balance.
• Dysregulated glutamate transport is implicated in CNS disorders, cancer metabolism, and oxidative stress-related pathology.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal testing of genes involved in L-glutamate import across the plasma membrane [1,2].
Description
L-glutamate import across plasma membrane (GO:0098712) is a biological process defined as the directed movement of L-glutamate from outside of a cell, across the plasma membrane, and into the cytosol. This process is fundamental because L-glutamate is not only a building block for protein synthesis but also a key excitatory neurotransmitter and a central metabolite in nitrogen and carbon metabolism. In the mammalian central nervous system, precise control of extracellular glutamate levels depends on transport systems that move glutamate across the plasma membrane, including the cystine/glutamate antiporter system xc-. In plants, analogous transport activities at the tonoplast can affect fruit amino acid composition, demonstrating that glutamate movement across membranes is a conserved feature of eukaryotic physiology. Researchers study GO:0098712 to understand how cells acquire glutamate, how transport contributes to signaling and metabolism, and how its dysfunction contributes to disease [1,2].
L-glutamate import across plasma membrane At A Glance
| GO ID | GO:0098712 |
|---|---|
| GO term | L-glutamate import across plasma membrane |
| Ontology | biological_process |
| Synonym | L-glutamate(1-) import across plasma membrane; L-glutamate(1-) import into cell; L-glutamate import into cell |
| Major function | Directed movement of L-glutamate from outside the cell, across the plasma membrane, into the cytosol |
| Directionality | Import (extracellular to intracellular) |
| Compartment | Plasma membrane and cytosol |
| Substrate | L-glutamate (L-glutamate(1-)) |
| Related transport systems | System xc- cystine/glutamate antiporter; plant tonoplast Glu/Asp/GABA exchangers |
What Is GO:0098712?
GO:0098712 is defined by QuickGO as the directed movement of L-glutamate from outside of a cell, across the plasma membrane and into the cytosol. In other words, it is the import of L-glutamate into the cell interior, spanning the plasma membrane. Synonyms include L-glutamate(1-) import across plasma membrane, L-glutamate(1-) import into cell, and L-glutamate import into cell. The process is a biological_process and is distinct from intracellular glutamate transport or vesicular glutamate storage.
Why Is L-glutamate import across plasma membrane Important in Cell Biology?
L-glutamate import across the plasma membrane is important because it controls the availability of a molecule that serves simultaneously as a neurotransmitter, a metabolic intermediate, and a redox-linked substrate. In the CNS, system xc- mediates cystine uptake coupled to glutamate export/import, thereby influencing extracellular glutamate and glutathione synthesis. In plants, tonoplast Glu/Asp/GABA exchangers affect amino acid composition, showing that glutamate transport across membranes has broad physiological consequences. Consequently, understanding GO:0098712 helps explain normal physiology and provides a framework for studying disease mechanisms and therapeutic targets [1,2].
• Controls extracellular and intracellular L-glutamate levels, which affect neurotransmission and excitability.
• Supports cysteine uptake and glutathione synthesis via system xc-, linking glutamate transport to antioxidant defense.
• Contributes to metabolic fueling and nitrogen handling in cells.
• Influences amino acid composition in plant tissues through tonoplast exchangers.
• Provides a mechanistic entry point for studying CNS disorders linked to glutamate homeostasis.
• Is relevant to cancer biology because system xc- is expressed in tumors and affects redox balance.
• Offers targets for pharmacological modulation of glutamate transport.
• Can be studied with genetic models that alter transport proteins [1,2].
• Helps interpret how cells maintain glutamate gradients across the plasma membrane.
• Connects membrane transport to downstream signaling and stress responses.
What Happens During L-glutamate import across plasma membrane?
Substrate recognition at the plasma membrane
In simple terms: The cell first recognizes glutamate outside the membrane.
The process begins when L-glutamate in the extracellular space is recognized by a transport protein embedded in the plasma membrane. System xc- is a cystine/glutamate antiporter that couples cystine uptake to glutamate movement and is a well-characterized route for glutamate flux across the plasma membrane. This step determines whether glutamate can be moved into the cytosol.
Translocation across the lipid bilayer
In simple terms: The transporter moves glutamate through the membrane.
After recognition, the transporter undergoes conformational changes that translocate L-glutamate across the plasma membrane. In the case of system xc-, the exchange of cystine and glutamate is coupled, so glutamate movement is linked to cystine import. This translocation step is the core of GO:0098712.
Release into the cytosol
In simple terms: Glutamate is delivered into the cell interior.
Once across the membrane, L-glutamate is released into the cytosol, where it can enter metabolic pathways or contribute to signaling. The definition of GO:0098712 explicitly includes movement into the cytosol, distinguishing it from transport into other compartments.
Coupling to cellular metabolism and redox balance
In simple terms: Imported glutamate feeds into other cell processes.
Glutamate import is functionally coupled to cysteine uptake and glutathione synthesis via system xc-, linking GO:0098712 to redox homeostasis. In plants, tonoplast Glu/Asp/GABA exchangers influence amino acid composition, showing that glutamate transport across membranes can affect metabolic pools.
Regulation by transport protein expression and activity
In simple terms: The cell can adjust how much glutamate it imports.
The rate of L-glutamate import across the plasma membrane depends on the expression and activity of transport proteins such as system xc-. Changes in transporter levels or activity can alter glutamate flux and downstream processes, making this step a point of regulation.
Key Genes Involved in GO:0098712 L-glutamate import across plasma membrane
The following genes and proteins are directly or functionally linked to L-glutamate import across the plasma membrane based on the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC7A11 | Cystine/glutamate antiporter light chain of system xc- | Mediates cystine uptake coupled to glutamate flux; target for redox and cancer studies |
| SLC3A2 | Heavy chain partner of system xc- | Required for system xc- function at the plasma membrane |
| SLC1A1 | Excitatory amino acid transporter (EAAT3) family member | Contributes to glutamate transport across plasma membranes |
| SLC1A2 | Glutamate transporter (EAAT2) in CNS | Regulates extracellular glutamate; relevant to neurotransmission |
| SLC1A3 | Glutamate transporter (EAAT1) | Controls glutamate clearance in the CNS |
| GLS | Glutaminase converts glutamine to glutamate | Links glutamine metabolism to glutamate pools |
| GOT1 | Aspartate aminotransferase | Contributes to glutamate metabolism |
| GOT2 | Mitochondrial aspartate aminotransferase | Participates in glutamate-related metabolic pathways |
| GLUL | Glutamine synthetase | Converts glutamate to glutamine, affecting glutamate availability |
| GAD1 | Glutamate decarboxylase 1 | Converts glutamate to GABA; relevant to neurotransmitter balance |
| GAD2 | Glutamate decarboxylase 2 | Converts glutamate to GABA |
| SLC17A7 | Vesicular glutamate transporter 1 | Packages glutamate into vesicles; related to glutamate handling |
| SLC17A6 | Vesicular glutamate transporter 2 | Vesicular glutamate storage |
| GRM2 | Metabotropic glutamate receptor 2 | Responds to extracellular glutamate |
| GRIN1 | NMDA receptor subunit 1 | Glutamate-gated ion channel; downstream of glutamate signaling |
| SLC38A1 | System A glutamine transporter | Indirectly affects glutamate pools |
| SLC38A2 | System A glutamine transporter | Indirectly affects glutamate pools |
How Is L-glutamate import across plasma membrane Regulated?
L-glutamate import across the plasma membrane is regulated at multiple levels. The expression and activity of system xc- (SLC7A11/SLC3A2) influence the rate of cystine/glutamate exchange and thus glutamate flux. Because system xc- is linked to glutathione synthesis, oxidative stress and redox status can affect its functional importance. In plants, tonoplast Glu/Asp/GABA exchangers affect amino acid composition, indicating that transport activity is integrated with whole-plant metabolism. These examples show that regulation occurs through changes in transporter abundance, coupling to metabolic demand, and cellular redox state [1,2].
L-glutamate import across plasma membrane and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC7A11 | Cancer redox balance and cystine/glutamate exchange | Knockout or overexpression in cancer cell lines |
| SLC3A2 | System xc- function and glutamate flux | Knockout cell models |
| SLC1A2 | Glutamate homeostasis in CNS disorders | Point-mutation knock-in in neuronal models |
| GAD1 | GABA/glutamate balance in neuropsychiatric disease | Overexpression or knockout in neuronal cells |
| SLC17A7 | Vesicular glutamate storage and neurotransmission | Knock-in reporter models |
CNS disorders and glutamate excitotoxicity
System xc- is a cystine/glutamate antiporter that influences extracellular glutamate levels in the CNS. Dysregulation of glutamate transport can contribute to excitotoxic injury and is relevant to neurological and psychiatric conditions.
Cancer metabolism and redox balance
System xc- supports cystine uptake and glutathione synthesis, linking L-glutamate import across the plasma membrane to antioxidant defense in cancer cells. This makes glutamate transport pathways relevant to tumor redox biology.
Plant amino acid composition
A tonoplast Glu/Asp/GABA exchanger affects tomato fruit amino acid composition, showing that glutamate transport across membranes can influence nutritional quality in plants.
From L-glutamate import across plasma membrane-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC7A11 alter L-glutamate import across the plasma membrane? | CRISPR knockout cell line |
| Does a specific point mutation in SLC7A11 change transport activity? | Point-mutation knock-in |
| Can a tagged transporter be used to track localization? | Tagged knock-in |
| Does overexpression of SLC7A11 increase glutamate flux? | Overexpression cell model |
| Does a plant Glu/Asp/GABA exchanger affect amino acid composition? | Knockout or overexpression in plant models |
| Can system xc- activity be measured in live cells? | Fluorescent or radiolabeled transport assays |
How to Study the L-glutamate import across plasma membrane Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled glutamate uptake | Rate of L-glutamate import | Transport activity in cell lines |
| Fluorescent glutamate biosensors | Real-time glutamate flux | Live-cell imaging |
| CRISPR knockout | Loss-of-function effects on transport | Gene function studies |
| CRISPR point mutation | Effect of specific amino acid changes | Structure-function analysis |
| CRISPR knock-in tagging | Protein localization and interactions | Imaging and proteomics |
| Overexpression | Gain-of-function effects on glutamate import | Transport capacity studies |
| Metabolomics | Glutamate and related metabolites | Pathway analysis |
| Amino acid composition analysis | Plant tissue amino acid levels | Crop quality studies |
Transport assays
Radiolabeled or fluorescent glutamate uptake assays can measure the rate of L-glutamate import across the plasma membrane in cells expressing system xc- or other transporters.
Genetic perturbation with CRISPR
CRISPR knockout, point mutation, knock-in, and overexpression models allow causal testing of genes such as SLC7A11 and SLC3A2 in glutamate transport.
Metabolic and redox profiling
Because system xc- links glutamate flux to cystine uptake and glutathione synthesis, metabolomic and redox assays can reveal downstream consequences of altered transport.
Plant amino acid analysis
In plants, amino acid composition analysis of fruits or tissues can assess the impact of tonoplast Glu/Asp/GABA exchangers on glutamate-related metabolism.
How CRISPR Can Be Used to Study GO:0098712 L-glutamate import across plasma membrane
Knockout
CRISPR knockout of SLC7A11 or SLC3A2 can eliminate system xc- function and reduce L-glutamate import across the plasma membrane, enabling loss-of-function studies.
Point Mutation
Point mutations introduced into transport proteins can test the role of specific residues in substrate recognition or translocation during L-glutamate import.
Knock-in
Knock-in of tags or reporters allows visualization and biochemical isolation of transporters involved in L-glutamate import across the plasma membrane.
Overexpression
Overexpression of SLC7A11 or other transporters can increase glutamate import capacity and reveal downstream metabolic or redox effects.
How EDITGENE Supports L-glutamate import across plasma membrane Research
Researchers studying L-glutamate import across plasma membrane-related genes often need to determine whether a candidate gene is causally involved in transport, metabolism, or disease. EDITGENE provides CRISPR-based cell models and screening services to test these hypotheses directly.
Contact EDITGENE today to design your custom CRISPR model for L-glutamate import across plasma membrane research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NTSR1 Knockout HEK293 Cell Line | EDJ-KQ1594 | Human | 4923 | Details Get a Quote |
| SLC1A4 Knockout HEK293 Cell Line | EDJ-KQ2483 | Human | 6509 | Details Get a Quote |
| SLC1A3 Knockout HEK293 Cell Line | EDJ-KQ2547 | Human | 6507 | Details Get a Quote |
| SLC1A2 Knockout HEK293 Cell Line | EDJ-KQ2658 | Human | 6506 | Details Get a Quote |
| SLC1A1 Knockout HEK293 Cell Line | EDJ-KQ5760 | Human | 6505 | Details Get a Quote |
| SLC1A6 Knockout HEK293 Cell Line | EDJ-KQ5761 | Human | 6511 | Details Get a Quote |
| SLC1A4 Knockout HCT 116 Cell Line | EDJ-KQ23060 | Human | 6509 | Details Get a Quote |
| SLC1A4 Knockout HeLa Cell Line | EDJ-KQ23061 | Human | 6509 | Details Get a Quote |
| SLC1A1 Knockout A-549 Cell Line | EDJ-KQ29174 | Human | 6505 | Details Get a Quote |
| SLC1A1 Knockout HCT 116 Cell Line | EDJ-KQ29175 | Human | 6505 | Details Get a Quote |
| SLC1A1 Knockout HeLa Cell Line | EDJ-KQ29176 | Human | 6505 | Details Get a Quote |
| NTSR1 Knockout HCT 116 Cell Line | EDJ-KQ21278 | Human | 4923 | Details Get a Quote |
| SLC1A4 Knockout A-549 Cell Line | EDJ-KQ21699 | Human | 6509 | Details Get a Quote |
| SLC1A3 Knockout HCT 116 Cell Line | EDJ-KQ24577 | Human | 6507 | Details Get a Quote |
| SLC1A3 Knockout HeLa Cell Line | EDJ-KQ24578 | Human | 6507 | Details Get a Quote |
Frequently Asked Questions About L-glutamate import across plasma membrane
What is L-glutamate import across plasma membrane?
It is the biological process GO:0098712, defined as the directed movement of L-glutamate from outside a cell, across the plasma membrane, and into the cytosol.
What genes are involved in L-glutamate import across plasma membrane?
Key genes include SLC7A11 and SLC3A2, which form the cystine/glutamate antiporter system xc-, as well as other glutamate transporters such as SLC1A1, SLC1A2, and SLC1A3.
What is the role of system xc- in glutamate transport?
System xc- is a cystine/glutamate antiporter that couples cystine uptake to glutamate flux across the plasma membrane.
How is L-glutamate import across plasma membrane studied?
It is studied using transport assays, CRISPR knockout or overexpression models, metabolomics, and imaging approaches.
Why is L-glutamate import important for the brain?
It helps control extracellular glutamate levels, which affect neurotransmission and excitability.
Is L-glutamate import across plasma membrane linked to cancer?
Yes, system xc- supports cystine uptake and glutathione synthesis, linking glutamate transport to redox balance in cancer cells.
What is the GO ID for L-glutamate import across plasma membrane?
The GO ID is GO:0098712.
What are synonyms for GO:0098712?
Synonyms include L-glutamate(1-) import across plasma membrane, L-glutamate(1-) import into cell, and L-glutamate import into cell.
Do plants have L-glutamate transport across membranes?
Yes, a tonoplast Glu/Asp/GABA exchanger affects tomato fruit amino acid composition, indicating conserved glutamate transport across membranes.
Can CRISPR be used to study L-glutamate import?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models can test the function of genes involved in L-glutamate import across the plasma membrane.
Conclusion
GO:0098712, L-glutamate import across plasma membrane, is a fundamental biological process that controls glutamate availability for neurotransmission, metabolism, and redox balance. System xc- and related transporters provide mechanistic insight into how cells move glutamate across the plasma membrane. In plants, tonoplast exchangers show that glutamate transport across membranes has broad physiological relevance. CRISPR-based models and transport assays offer powerful ways to study this process and its role in health and disease [1,2].
References
- 1. Bridges RJ et al.. 2012. System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS.. Br J Pharmacol 165(1):20-34 PMID: 21564084
- 2. Snowden CJ et al.. 2015. A tonoplast Glu/Asp/GABA exchanger that affects tomato fruit amino acid composition.. Plant J 81(5):651-60 PMID: 25602029