GO:0098708 D-glucose import across plasma membrane: Transport Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0098708 describes the directed movement of D-glucose from outside a cell, across the plasma membrane, and into the cytosol.
• This process is mediated by facilitative glucose transporters (GLUT/SLC2A family) and sodium-coupled symporters (SGLT/SLC5A family) that move glucose down or against its concentration gradient.
• In plants, proton-driven carriers such as PMT5a and STP13 mediate plasma membrane glucose import, highlighting evolutionary conservation of the import mechanism.
• D-glucose import is critical for cellular energy supply, and its dysregulation is linked to cancer metabolic reprogramming and other pathologies.
• Facilitative transporters can function during ER transit, revealing that glucose import machinery is not restricted to the cell surface.
• Quantitative glucose and ATP sensing methods enable real-time measurement of import activity in living cells.
Description
D-glucose import across plasma membrane (GO:0098708) is the biological process by which D-glucose is transported from the extracellular space, across the plasma membrane, and into the cytosol. This process is fundamental to cellular energy metabolism, as glucose serves as a primary substrate for glycolysis and oxidative phosphorylation. The directed movement of glucose is mediated by specific membrane proteins that either facilitate diffusion down a concentration gradient or couple glucose uptake to ion gradients. Researchers study this process to understand metabolic regulation, nutrient sensing, and the molecular basis of diseases characterized by altered glucose handling. The ontology term GO:0098708 captures the vectorial nature of glucose import, distinguishing it from intracellular glucose trafficking or glucose export. In mammalian cells, facilitative transporters of the SLC2A (GLUT) family and sodium-dependent transporters of the SLC5A (SGLT) family are principal mediators of this process. In plants, proton-driven carriers such as PMT5a and STP13 perform analogous plasma membrane glucose import, underscoring the evolutionary conservation of this transport function. The process is also relevant to specialized cell types, including laticifer protoplasts, where multiple sugar uptake systems have been documented.
D-glucose import across plasma membrane At A Glance
| GO ID | GO:0098708 |
|---|---|
| GO term | D-glucose import across plasma membrane |
| Ontology | biological_process |
| Synonym | glucose import across plasma membrane; glucose import into cell; high affinity glucose import |
| Major function | Directed transport of D-glucose from the extracellular space into the cytosol across the plasma membrane |
| Cellular location | Plasma membrane |
| Representative transporters | SLC2A (GLUT) facilitative transporters; SLC5A (SGLT) sodium-coupled symporters; plant PMT5a and STP13 proton-driven carriers |
| Directionality | Inward (extracellular to cytosolic) |
| Substrate | D-glucose |
What Is GO:0098708?
GO:0098708 is defined as the directed movement of D-glucose from outside of a cell, across the plasma membrane and into the cytosol. It encompasses the translocation step itself, regardless of whether the transport is driven by facilitated diffusion or by coupling to an ion gradient. The term is a biological process and is synonymous with glucose import across plasma membrane, glucose import into cell, and high affinity glucose import.
Why Is D-glucose import across plasma membrane Important in Cell Biology?
D-glucose import across the plasma membrane is a rate-limiting step for cellular glucose utilization and thus directly influences energy production, biosynthetic precursor supply, and metabolic signaling. Because glucose is a primary fuel and carbon source, its import is essential for normal cell physiology and is frequently reprogrammed in disease states such as cancer, where increased glucose uptake supports rapid proliferation. Understanding the molecular players and regulatory mechanisms of this process is therefore central to metabolism research, drug target discovery, and the development of diagnostic tools based on glucose sensing.
• Provides the first committed step for glucose entry into glycolysis and oxidative phosphorylation.
• Determines cellular energy status and ATP production capacity.
• Is reprogrammed in cancer to support anabolic growth and survival.
• Involves transporters that are targets for metabolic disease and cancer therapy.
• Plant proton-driven glucose import supports sink organ filling and crop yield.
• Facilitative transporters can operate during ER transit, affecting membrane protein biogenesis.
• Sodium-coupled glucose import links ion gradients to nutrient uptake in epithelia.
• Quantitative sensing of glucose import enables real-time metabolic phenotyping.
• Altered glucose transport contributes to the ionic microenvironment of tumors.
• Multiple sugar uptake systems exist in specialized plant cells, indicating functional diversity.
What Happens During D-glucose import across plasma membrane?
Recognition and binding of extracellular D-glucose
In simple terms: The transporter protein on the cell surface grabs a glucose molecule from outside the cell.
The process begins when a plasma membrane transporter binds D-glucose from the extracellular environment. Facilitative transporters of the SLC2A family and sodium-coupled symporters of the SLC5A family recognize glucose with stereospecificity, ensuring that the D-isomer is preferentially transported. In plants, proton-driven carriers such as PMT5a and STP13 similarly bind glucose before translocation. Binding triggers conformational changes that initiate the transport cycle.
Translocation across the lipid bilayer
In simple terms: The transporter changes shape to carry glucose through the membrane and release it inside the cell.
Following substrate binding, the transporter undergoes a series of conformational transitions that move glucose across the lipid bilayer. For facilitative transporters, this occurs via an alternating access mechanism driven by the glucose concentration gradient. For sodium-coupled symporters, the inward translocation of glucose is energetically coupled to the inward movement of Na+ ions down their electrochemical gradient. The vectorial nature of this step defines the import process captured by GO:0098708.
Release of D-glucose into the cytosol
In simple terms: Once inside, the transporter lets go of the glucose so it can be used by the cell.
After crossing the membrane, the transporter releases D-glucose into the cytosol. This step completes the import event and makes glucose available for immediate metabolic processing, including phosphorylation by hexokinase and entry into glycolysis. The release step is essential for maintaining a favorable gradient for continued import and for preventing intracellular glucose accumulation that could feedback-inhibit transport.
Energetics and driving forces
In simple terms: Some transporters use the natural flow of glucose, while others use the flow of sodium ions to pull glucose in.
D-glucose import can be driven by different energetic mechanisms. Facilitative transporters mediate passive downhill transport, whereas sodium-coupled symporters use the Na+ gradient maintained by the Na+/K+-ATPase to drive glucose uptake against its own concentration gradient. In plants, proton-driven carriers couple glucose import to the proton motive force. These distinct energetics allow cells to import glucose under a range of extracellular concentrations.
Regulation of transporter availability at the plasma membrane
In simple terms: Cells control how much glucose they take in by moving transporters to or away from the surface.
The rate of D-glucose import is regulated by the abundance of transporters at the plasma membrane. Facilitative transporters can function during ER transit, indicating that trafficking and membrane insertion are important control points. Hormonal and metabolic signals influence the translocation of glucose transporters to the cell surface, thereby modulating import capacity. Quantitative glucose sensing methods have been developed to measure these dynamic changes in living cells.
Key Genes Involved in GO:0098708 D-glucose import across plasma membrane
The following genes encode proteins directly involved in or regulating D-glucose import across the plasma membrane.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC2A1 (GLUT1) | Facilitative glucose transporter mediating basal glucose import | Widely studied in cancer metabolism and blood-brain barrier transport |
| SLC2A2 (GLUT2) | Facilitative transporter with high capacity for glucose import | Relevant to hepatic and pancreatic glucose sensing |
| SLC2A3 (GLUT3) | High-affinity facilitative glucose transporter | Important for neuronal glucose uptake |
| SLC2A4 (GLUT4) | Insulin-responsive facilitative glucose transporter | Key target in diabetes and insulin resistance research |
| SLC5A1 (SGLT1) | Sodium-coupled glucose symporter | Studied in intestinal glucose absorption and epithelial transport |
| SLC5A2 (SGLT2) | Sodium-coupled glucose symporter in kidney | Therapeutic target for diabetes via SGLT2 inhibitors |
| PMT5a | Plant proton-driven glucose carrier | Model for plasma membrane glucose import in sink tissues |
| STP13 | Plant proton-driven glucose carrier | Studied in sugar beet taproot glucose import |
| HK1 | Hexokinase that phosphorylates imported glucose | Links glucose import to glycolytic flux |
| HK2 | Hexokinase isoform associated with high glucose consumption | Marker of cancer metabolic reprogramming |
| ATP1A1 | Na+/K+-ATPase maintaining Na+ gradient for symport | Provides driving force for sodium-coupled glucose import |
| SLC2A5 (GLUT5) | Fructose transporter with minor glucose transport activity | Used as a comparative control in sugar transport studies |
| SLC2A6 (GLUT6) | Facilitative glucose transporter | Investigated in metabolic and immune cell contexts |
| SLC2A8 (GLUT8) | Intracellular and plasma membrane glucose transporter | Studied in testis and brain glucose handling |
| SLC2A12 (GLUT12) | Facilitative glucose transporter | Explored in cancer and insulin-sensitive tissues |
| TBC1D4 (AS160) | Regulator of GLUT4 translocation | Key node in insulin signaling and glucose import regulation |
| SLC5A4 (SGLT3) | Glucose sensor rather than transporter | Used to dissect sensing versus transport functions |
How Is D-glucose import across plasma membrane Regulated?
D-glucose import across the plasma membrane is regulated at multiple levels. Hormonal signals such as insulin promote the translocation of GLUT4-containing vesicles to the plasma membrane, increasing import capacity in muscle and adipose tissue. The Na+/K+-ATPase maintains the sodium gradient that drives sodium-coupled glucose import, and its activity therefore indirectly regulates SGLT-mediated uptake. In plants, proton-driven carriers are regulated by the proton motive force and developmental cues. Additionally, facilitative transporters can function during ER transit, suggesting that trafficking and quality control pathways influence the amount of transporter reaching the cell surface. Quantitative glucose and ATP sensing approaches have been used to monitor these regulatory dynamics in real time.
D-glucose import across plasma membrane and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC2A1 (GLUT1) | Cancer metabolic reprogramming; blood-brain barrier transport defects | Knockout and overexpression cell lines; glucose uptake assays |
| SLC2A4 (GLUT4) | Type 2 diabetes and insulin resistance | Insulin-stimulated translocation models in adipocytes and myotubes |
| SLC5A2 (SGLT2) | Diabetes mellitus; renal glucose reabsorption | SGLT2 inhibitor studies in kidney epithelial cells |
| SLC5A1 (SGLT1) | Intestinal glucose absorption disorders | Knockout intestinal cell models and transport assays |
| PMT5a/STP13 | Plant sink strength and sugar allocation | Plant knockout and overexpression lines for taproot glucose import |
Cancer metabolism and glucose import
Many cancers exhibit increased glucose uptake to support rapid proliferation, a phenomenon often linked to overexpression of facilitative glucose transporters such as GLUT1. The endoplasmic reticulum plays a pivotal role in cancer glucose metabolism, influencing the supply of glucose-derived intermediates for biosynthetic pathways. Altered glucose import also contributes to the ionic microenvironment of breast tumors, where sodium channels and transporters shape the extracellular milieu. Targeting glucose import pathways is therefore an active area of anticancer research.
Metabolic disorders and glucose transport
Dysregulated glucose import is central to metabolic disorders including diabetes, where impaired insulin-stimulated GLUT4 translocation reduces glucose uptake in peripheral tissues. Sodium-coupled glucose transporters in the kidney, particularly SGLT2, are validated therapeutic targets for lowering blood glucose. Understanding the molecular basis of these transport defects informs the development of pharmacological interventions.
Neurological and specialized tissue functions
The brain depends on efficient glucose import across the blood-brain barrier and into neurons, processes mediated by facilitative transporters such as GLUT1 and GLUT3. Disruptions in these transport systems can affect neuronal energy supply and are studied in the context of neurological disease. In plants, proton-driven glucose import supports sink organ filling, and its manipulation has implications for crop productivity.
From D-glucose import across plasma membrane-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate transporter required for D-glucose import? | CRISPR knockout cell line followed by glucose uptake assay |
| Does a point mutation alter transport kinetics? | Point-mutation knock-in cell line expressing mutant transporter |
| Can a tagged transporter be tracked to the plasma membrane? | Tagged knock-in with fluorescent protein for live imaging |
| Does overexpression increase glucose import capacity? | Overexpression cell line with quantitative glucose sensing |
| Which genes regulate transporter trafficking? | CRISPR library screening with glucose import readout |
| How does glucose import affect tumor metabolism? | Cancer cell models with transporter knockout and metabolic profiling |
How to Study the D-glucose import across plasma membrane Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescent glucose analog uptake | Rate of D-glucose import | Transporter knockout and overexpression phenotyping |
| Genetically encoded glucose sensors | Intracellular glucose concentration dynamics | Real-time metabolic sensing in live cells |
| ATP sensing | Cellular energy status linked to glucose import | Coupling of import to energy production |
| Live-cell imaging of tagged transporters | Subcellular localization and trafficking | Plasma membrane versus ER distribution |
| Electrophysiology in plant protoplasts | Sugar-induced transport currents | Characterization of proton-driven carriers |
| Radiolabeled glucose flux | Unidirectional transport rate | Kinetic analysis of facilitative and sodium-coupled transporters |
| CRISPR library screening | Genes required for glucose import | Discovery of novel regulators |
| Metabolic profiling | Downstream metabolites of imported glucose | Linking import to cancer metabolism |
Quantitative glucose and ATP sensing
Quantitative glucose and ATP sensing in mammalian cells allows real-time measurement of import activity and its coupling to energy status. These methods use genetically encoded or chemical sensors to report intracellular glucose and ATP concentrations, enabling researchers to dissect transport kinetics and regulation.
Transport assays in cell models
Radiolabeled or fluorescent glucose analogs are used to measure import rates in cultured cells. Such assays can distinguish between facilitative and sodium-coupled transport based on inhibitor sensitivity and ion dependence. They are widely applied to characterize transporter knockout and overexpression models.
Imaging of transporter localization
Fluorescence imaging of tagged transporters reveals their subcellular distribution, including plasma membrane localization and ER transit. This approach is valuable for studying how trafficking regulates glucose import capacity.
Plant sugar uptake measurements
In plants, protoplast-based sugar uptake assays and electrophysiology have been used to demonstrate multiple sugar uptake systems across the plasma membrane. These methods support functional characterization of proton-driven glucose carriers such as PMT5a and STP13.
How CRISPR Can Be Used to Study GO:0098708 D-glucose import across plasma membrane
Knockout
CRISPR knockout of candidate glucose transporter genes, such as SLC2A1 or SLC5A1, enables loss-of-function studies to determine whether a specific transporter is required for D-glucose import. Knockout cell lines can be subjected to glucose uptake assays and metabolic profiling to quantify the contribution of each transporter.
Point Mutation
Point-mutation knock-in can be used to introduce specific amino acid substitutions into transporter genes to test structure-function relationships, such as residues involved in substrate binding or ion coupling. These models help dissect the molecular determinants of transport activity and specificity.
Knock-in
Tagged knock-in of endogenous transporter loci with fluorescent or affinity tags allows visualization and purification of the transporter in its native context. This approach is useful for studying trafficking, membrane insertion, and ER transit of glucose transporters.
Overexpression
Overexpression of wild-type or mutant transporters in cell lines increases glucose import capacity and can be used to study transport kinetics and downstream metabolic effects. Overexpression models are also valuable for testing pharmacological inhibitors of glucose import.
How EDITGENE Supports D-glucose import across plasma membrane Research
Researchers studying D-glucose import across plasma membrane-related genes often need to determine whether a candidate gene is causally involved in transport, how mutations affect transporter function, and where the protein localizes within the cell. EDITGENE provides a comprehensive suite of CRISPR-based services to address these questions with precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for D-glucose import across plasma membrane research.
Frequently Asked Questions About D-glucose import across plasma membrane
What is D-glucose import across plasma membrane?
It is the biological process (GO:0098708) by which D-glucose moves from outside a cell, across the plasma membrane, and into the cytosol.
What genes are involved in D-glucose import across plasma membrane?
Key genes include SLC2A1 (GLUT1), SLC2A4 (GLUT4), SLC5A1 (SGLT1), SLC5A2 (SGLT2), and in plants PMT5a and STP13.
What is the GO ID for D-glucose import across plasma membrane?
The GO ID is GO:0098708.
How is D-glucose import measured in cells?
It can be measured using fluorescent glucose analogs, radiolabeled glucose flux, or genetically encoded glucose sensors.
What is the difference between facilitative and sodium-coupled glucose import?
Facilitative transporters move glucose down its concentration gradient, while sodium-coupled symporters use the Na+ gradient to drive uptake against the glucose gradient.
Why is D-glucose import important in cancer?
Many cancers increase glucose import to support rapid growth, often through overexpression of transporters such as GLUT1.
Can CRISPR be used to study glucose transporters?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to study transporter function and regulation.
What is the role of the plasma membrane in glucose import?
The plasma membrane is the barrier across which transporters move glucose into the cytosol, defining the import step of GO:0098708.
Do plants have D-glucose import across plasma membrane?
Yes, plants use proton-driven carriers such as PMT5a and STP13 for plasma membrane glucose import.
What methods study glucose import regulation?
Quantitative glucose and ATP sensing, live-cell imaging of tagged transporters, and transport assays are commonly used.
Conclusion
D-glucose import across plasma membrane (GO:0098708) is a fundamental biological process that governs cellular glucose supply and energy metabolism. Its molecular mediators, including facilitative and sodium-coupled transporters, are central to normal physiology and are frequently altered in cancer and metabolic disorders. Continued research using CRISPR models and quantitative sensing methods will further clarify how this process is regulated and how it can be targeted therapeutically.
References
- 1. Reyer A et al.. 2024. Sugar beet PMT5a and STP13 carriers suitable for proton-driven plasma membrane sucrose and glucose import in taproots.. Plant J 118(6):2219-2232 PMID: 38602250
- 3. Carbó R et al.. 2023. Relevance of Sugar Transport across the Cell Membrane.. Int J Mol Sci 24(7) PMID: 37047055
- 4. Marini C et al.. 2026. The pivotal role of endoplasmic reticulum in cancer glucose metabolism.. iScience 29(1):114503 PMID: 41561377
- 5. Takanaga H et al.. 2010. Facilitative plasma membrane transporters function during ER transit.. FASEB J 24(8):2849-58 PMID: 20354141
- 6. Liemburg-Apers DC et al.. 2011. Quantitative glucose and ATP sensing in mammalian cells.. Pharm Res 28(11):2745-57 PMID: 21691894
- 7. Leslie TK et al.. 2023. Sodium channels and the ionic microenvironment of breast tumours.. J Physiol 601(9):1543-1553 PMID: 36183245
- 8. Bouteau F et al.. 1999. Evidence of multiple sugar uptake across the plasma membrane of laticifer protoplasts from Hevea.. Bioelectrochem Bioenerg 48(1):135-9 PMID: 10228580
