GO:1901480 oleate transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1901480 (oleate transmembrane transporter activity) is a molecular function that enables the transfer of oleate, a monounsaturated fatty acid, from one side of a membrane to the other.
• CD36 is a well-characterized membrane protein that facilitates oleate uptake and transport, and its activity influences lipid metabolism, inflammation, and cell survival.
• Oleate transport is linked to peroxisomal and lysosomal lipid handling, with proteins such as ABCD1 and NPC1 contributing to fatty acid trafficking across membranes.
• Dysregulated oleate transport contributes to metabolic diseases including nonalcoholic steatohepatitis (NASH), spinal cord injury, and cancer progression.
• Experimental models for studying oleate transport include CRISPR knockout, point mutation, and overexpression of candidate transporters in cell lines and animal models.
• Key methods to investigate oleate transmembrane transporter activity include fluorescent fatty acid uptake assays, lipidomics, and chemoproteomic profiling.
Description
Oleate, the salt of oleic acid (18:1 n-9), is the most abundant monounsaturated fatty acid in human tissues and a central player in lipid metabolism, membrane homeostasis, and energy storage. The molecular function defined by GO:1901480, oleate transmembrane transporter activity, enables the transfer of oleate from one side of a membrane to the other. This activity is essential for cellular uptake of dietary oleate, its distribution among organelles, and its utilization in processes such as beta-oxidation, lipid droplet formation, and membrane biogenesis. Research into oleate transmembrane transporter activity has gained prominence because dysregulated fatty acid transport is a hallmark of metabolic disorders, including nonalcoholic steatohepatitis (NASH), obesity, and insulin resistance. Moreover, oleate transport influences immune cell function, as shown by studies linking CD36-mediated oleate uptake to microglial lipophagy and spinal cord injury outcomes. In cancer, oleate uptake supports proliferation and survival, making transporters attractive therapeutic targets. Understanding the molecular players, regulatory mechanisms, and disease relevance of oleate transmembrane transporter activity is therefore critical for both basic cell biology and translational medicine. This article synthesizes current knowledge based on QuickGO annotation and verified PubMed literature, providing a resource for researchers designing CRISPR-based experiments to dissect this function.
oleate transmembrane transporter activity At A Glance
| GO ID | GO:1901480 |
|---|---|
| GO term | oleate transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | oleate transporter activity |
| Definition | Enables the transfer of oleate from one side of a membrane to the other. |
| Major function | Facilitated diffusion or active transport of oleate across lipid bilayers |
| Related processes | Fatty acid uptake, lipid homeostasis, energy metabolism |
| Representative genes | CD36, SLC27A1, ACSL1, ABCD1, NPC1 |
| Disease associations | Nonalcoholic steatohepatitis, spinal cord injury, cancer |
What Is GO:1901480?
Oleate transmembrane transporter activity (GO:1901480) is a molecular function that enables the directed movement of oleate, a monounsaturated fatty acid anion, across a biological membrane. This activity is typically mediated by integral membrane proteins that facilitate the passage of oleate from the extracellular space to the cytoplasm, or between intracellular compartments, without necessarily requiring ATP hydrolysis. It is distinct from fatty acid oxidation or esterification, focusing solely on the transport step.
Why Is oleate transmembrane transporter activity Important in Cell Biology?
Oleate transmembrane transporter activity is fundamental to cellular lipid metabolism because it controls the availability of oleate for energy production, membrane synthesis, and signaling. Dysregulation of this activity leads to excessive lipid accumulation (steatosis), lipotoxicity, and inflammation, which are central to metabolic diseases such as NASH and type 2 diabetes. In the nervous system, CD36-mediated oleate transport affects microglial function and recovery after spinal cord injury. In cancer, oleate uptake supports rapid proliferation and survival, and its inhibition can reduce tumor growth. Thus, understanding and manipulating oleate transporters has broad therapeutic potential.
• Regulates cellular uptake of dietary oleate, influencing energy balance and lipid storage.
• Modulates membrane fluidity and lipid raft composition, affecting signal transduction.
• Contributes to peroxisomal and mitochondrial fatty acid oxidation through transport into organelles.
• Plays a role in immune cell function, including microglial lipophagy and inflammation resolution.
• Is implicated in nonalcoholic steatohepatitis (NASH) pathogenesis via lipid overload.
• Supports cancer cell proliferation by providing fatty acids for membrane synthesis.
• Affects drug delivery and bioavailability of lipophilic compounds.
• Serves as a target for chemoproteomic profiling of nitro-fatty acid interactions.
• Influences lysosomal lipid trafficking and cholesterol homeostasis via NPC1.
• Provides a mechanistic link between diet, genetics, and metabolic disease risk.
Molecular Mechanism of oleate transmembrane transporter activity
Substrate recognition and binding
In simple terms: The transporter first grabs oleate from one side of the membrane.
Oleate transporters such as CD36 possess a hydrophobic pocket that accommodates long-chain fatty acids. CD36 binds oleate with high affinity, and this binding is essential for subsequent transport. The interaction involves electrostatic and hydrophobic forces, and may be regulated by post-translational modifications. For example, CD36 palmitoylation affects its membrane localization and function.
Membrane translocation
In simple terms: The transporter moves oleate across the lipid bilayer.
After binding, the transporter undergoes conformational changes that allow oleate to traverse the membrane. For CD36, this process is thought to involve a flip-flop mechanism or a channel-like passage. In peroxisomal ABC transporters such as ABCD1, oleate is translocated into peroxisomes for beta-oxidation, a process that requires ATP hydrolysis. The exact stoichiometry and energy coupling vary among transporters.
Intracellular release and trafficking
In simple terms: Once inside, oleate is handed off to other proteins.
Following translocation, oleate is rapidly bound by intracellular fatty acid-binding proteins (FABPs) and acyl-CoA synthetases (ACSLs), which convert it to oleoyl-CoA for metabolic pathways. This prevents retrograde diffusion and maintains a concentration gradient. In lysosomes, NPC1 facilitates the export of oleate and other lipids, and its dysfunction leads to lipid accumulation.
Regulation by cellular signals
In simple terms: The cell can speed up or slow down oleate transport based on its needs.
Oleate transport activity is regulated by hormones, nutrients, and inflammatory signals. Insulin promotes CD36 translocation to the plasma membrane, enhancing oleate uptake. In contrast, AMPK activation reduces CD36 expression and fatty acid transport. Nitro-fatty acids can covalently modify CD36 and other proteins, potentially altering transport activity. These regulatory layers ensure that oleate flux matches cellular demand.
Key Genes Involved in GO:1901480 oleate transmembrane transporter activity
The following genes encode proteins that directly or indirectly mediate oleate transmembrane transporter activity, as supported by published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD36 | Facilitates oleate uptake across plasma membrane | Knockout reduces oleate transport; linked to spinal cord injury and NASH |
| SLC27A1 | Fatty acid transport protein 1; mediates oleate uptake | Overexpression increases oleate influx; target for metabolic studies |
| ACSL1 | Converts oleate to oleoyl-CoA after transport | Knockdown alters lipid metabolism; used in lipidomics |
| ABCD1 | Peroxisomal ABC transporter for very long-chain fatty acids | Mutations cause X-linked adrenoleukodystrophy; oleate transport affected |
| NPC1 | Lysosomal membrane protein involved in lipid export | Deficiency causes Niemann-Pick type C; affects oleate trafficking |
| FABP4 | Intracellular fatty acid binding protein | Binds oleate; knockout affects lipid signaling |
| FABP5 | Intracellular fatty acid binding protein | Binds oleate; involved in cancer progression |
| SLC27A4 | Fatty acid transport protein 4 | Mediates oleate uptake in intestine; relevant to absorption |
| DGAT1 | Diacylglycerol O-acyltransferase 1 | Esterifies oleoyl-CoA into triglycerides; affects storage |
| CPT1A | Carnitine palmitoyltransferase 1A | Transports oleoyl-CoA into mitochondria for oxidation |
| PPARA | Peroxisome proliferator-activated receptor alpha | Regulates expression of fatty acid transporters |
| SREBF1 | Sterol regulatory element-binding transcription factor 1 | Controls lipogenic genes including CD36 |
| NR1H3 | Liver X receptor alpha | Regulates lipid transporters and efflux |
| ORCTL3 | Organic cation transporter like-3 | May transport oleate; anticancer gene |
| HMOX1 | Heme oxygenase 1 | Indirectly affects lipid transport via oxidative stress |
| MAP1LC3B | Autophagy marker; involved in lipophagy | Linked to CD36-mediated lipophagy |
| LAMP1 | Lysosomal-associated membrane protein 1 | Marker for lysosomal lipid trafficking |
How Is oleate transmembrane transporter activity Regulated?
Oleate transmembrane transporter activity is regulated at multiple levels. Transcriptional control involves nuclear receptors such as PPARA and SREBF1, which modulate the expression of CD36 and other transporters in response to fatty acid availability. Post-translational modifications, including palmitoylation and phosphorylation, affect CD36 membrane localization and activity. Hormonal signals like insulin promote CD36 translocation to the plasma membrane, while AMPK activation inhibits it. Additionally, nitro-fatty acids can covalently modify CD36 and other proteins, potentially altering transport function. These regulatory mechanisms ensure that oleate flux is tightly coupled to cellular metabolic demands.
oleate transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CD36 | Nonalcoholic steatohepatitis, spinal cord injury | CD36 knockout mice; primary microglia |
| NPC1 | Niemann-Pick type C disease | NPC1 mutant fibroblasts; CRISPR knock-in |
| ABCD1 | X-linked adrenoleukodystrophy | ABCD1 knockout cell lines; peroxisomal transport assays |
| FABP5 | Cancer progression | FABP5 overexpression in cancer cell lines |
| ORCTL3 | Cancer cell death | ORCTL3 knockout and overexpression |
Oleate transport in nonalcoholic steatohepatitis (NASH)
Nonalcoholic steatohepatitis is characterized by excessive hepatic lipid accumulation, inflammation, and fibrosis. CD36-mediated oleate uptake contributes to steatosis, and its expression is upregulated in NASH patients. Machine learning analyses have identified CD36 and related genes as disease-specific markers associated with immune infiltration in NASH. Inhibiting oleate transport may reduce lipid overload and inflammation, making it a therapeutic target.
Oleate transport in spinal cord injury
After spinal cord injury, microglia accumulate lipids and undergo lipophagy. CD36 facilitates oleate uptake, and its inhibition accelerates microglial lipophagy, reducing neuroinflammation and improving recovery in mouse models. This highlights the role of oleate transport in neuroinflammatory diseases.
Oleate transport in cancer
Cancer cells often upregulate fatty acid transporters to support rapid proliferation. CD36 and FABP5 mediate oleate uptake, which can promote cell survival and metastasis. Targeting oleate transport may therefore be a viable anticancer strategy, as suggested by studies on endocannabinoid system modulation.
Oleate transport in lysosomal storage disorders
Niemann-Pick type C disease is caused by mutations in NPC1, leading to defective lysosomal export of lipids including oleate. This results in lipid accumulation and neurodegeneration. Studying oleate transport in NPC1-deficient cells can provide insights into disease mechanisms and potential therapies.
From oleate transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CD36 mediate oleate uptake in microglia? | CD36 knockout mice or CRISPR knockout BV-2 cells |
| What is the role of NPC1 in lysosomal oleate export? | NPC1 point mutation knock-in cells |
| Can overexpression of SLC27A1 increase oleate transport? | SLC27A1 overexpression in HEK293 cells |
| How does ABCD1 mutation affect peroxisomal oleate transport? | ABCD1 knockout or point mutation in fibroblasts |
| Does ORCTL3 transport oleate and induce apoptosis? | ORCTL3 knockout and overexpression in cancer cells |
| What is the impact of CD36 palmitoylation on oleate transport? | CD36 palmitoylation-deficient knock-in mice |
How to Study the oleate transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| BODIPY-oleate uptake | Rate of oleate transport into cells | Screening for transporters; validating CD36 |
| Lipidomics (LC-MS) | Oleate and metabolite levels | Quantifying transport impact on lipidome |
| Chemoproteomics | Protein targets of oleate derivatives | Identifying novel transporters |
| CRISPR knockout screen | Genes affecting oleate uptake | Discovery of transport regulators |
| Western blot | Protein expression of transporters | Validating knockout efficiency |
| Immunofluorescence | Subcellular localization of transporters | Studying membrane trafficking |
| RNA-seq | Transcriptional changes upon transport modulation | Identifying regulatory networks |
| Lipophagy assay | Autophagic flux in response to oleate | Studying CD36 in microglia |
Fluorescent fatty acid uptake assays
Fluorescently labeled oleate analogs, such as BODIPY-oleate, are used to measure transport activity in live cells. This method allows real-time visualization and quantification of oleate uptake, and can be combined with CRISPR knockout of candidate transporters to confirm specificity.
Lipidomics and mass spectrometry
Mass spectrometry-based lipidomics quantifies oleate and its metabolites in cells and tissues. By comparing wild-type and transporter knockout cells, researchers can determine the contribution of specific proteins to oleate transport and metabolism.
Chemoproteomic profiling
Chemoproteomic approaches using activity-based probes can identify proteins that interact with oleate and its derivatives. For example, nitro-fatty acids have been used to profile cellular targets, revealing CD36 and other proteins involved in oleate transport.
Genetic screens and CRISPR libraries
CRISPR knockout libraries enable unbiased screening for genes that regulate oleate transport. Cells are incubated with fluorescent oleate, and transporters are identified by altered uptake. This approach can uncover novel regulators and validate known genes like CD36.
How CRISPR Can Be Used to Study GO:1901480 oleate transmembrane transporter activity
Knockout
CRISPR knockout of candidate oleate transporters such as CD36 or SLC27A1 is used to abolish transport activity and assess downstream effects on lipid metabolism, inflammation, and cell survival. For example, CD36 knockout mice show reduced oleate uptake and altered microglial function after spinal cord injury.
Point Mutation
Point mutations can be introduced to dissect specific residues required for oleate binding or translocation. For instance, mutating palmitoylation sites on CD36 can reveal their role in membrane localization and transport activity. Similarly, disease-causing mutations in NPC1 can be modeled to study lysosomal oleate export.
Knock-in
Knock-in of tagged transporters (e.g., GFP-CD36) allows real-time imaging of oleate transport dynamics and protein trafficking. This approach can also be used to express mutant transporters under endogenous promoters to study physiological regulation.
Overexpression
Overexpression of oleate transporters in cell lines such as HEK293 or HepG2 increases oleate uptake and can be used to study transport kinetics, substrate specificity, and downstream metabolic effects. For example, SLC27A1 overexpression enhances oleate influx and lipid accumulation.
How EDITGENE Supports oleate transmembrane transporter activity Research
Researchers studying oleate transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in oleate transport, how mutations affect function, and what downstream pathways are engaged. EDITGENE provides a comprehensive suite of CRISPR-based services to address these questions, from generating knockout cell lines to performing high-throughput library screens.
Contact EDITGENE today to design your custom CRISPR model for oleate transmembrane transporter activity research.
Frequently Asked Questions About oleate transmembrane transporter activity
What is oleate transmembrane transporter activity?
It is a molecular function (GO:1901480) that enables the transfer of oleate, a monounsaturated fatty acid, from one side of a membrane to the other.
What genes are involved in oleate transmembrane transporter activity?
Key genes include CD36, SLC27A1, ACSL1, ABCD1, and NPC1, which encode proteins that facilitate or regulate oleate transport.
How is oleate transport measured in the lab?
Common methods include fluorescent BODIPY-oleate uptake assays, lipidomics, and chemoproteomic profiling.
What diseases are linked to oleate transport dysfunction?
Nonalcoholic steatohepatitis, spinal cord injury, cancer, and Niemann-Pick type C disease are associated with altered oleate transport.
What is the role of CD36 in oleate transport?
CD36 is a membrane glycoprotein that binds and facilitates the uptake of oleate and other long-chain fatty acids.
Can CRISPR be used to study oleate transporters?
Yes, CRISPR knockout, point mutation, and overexpression models are widely used to dissect the function of oleate transporters.
What is the difference between oleate transport and fatty acid oxidation?
Oleate transport moves oleate across membranes, while fatty acid oxidation breaks it down for energy; transport is a prerequisite for oxidation.
Which organelles are involved in oleate transport?
The plasma membrane, peroxisomes, and lysosomes are key sites, with transporters like CD36, ABCD1, and NPC1 mediating oleate movement.
How does oleate transport affect inflammation?
Oleate uptake via CD36 can modulate microglial lipophagy and inflammatory responses, as shown in spinal cord injury models.
What experimental models are available for oleate transport research?
Models include knockout mice, CRISPR-edited cell lines, and overexpression systems for genes like CD36, SLC27A1, and NPC1.
Conclusion
Oleate transmembrane transporter activity (GO:1901480) is a critical molecular function that governs cellular fatty acid uptake and distribution. Dysregulation of this activity contributes to metabolic, inflammatory, and neurodegenerative diseases, making it a promising therapeutic target. Advances in CRISPR-based models and analytical methods are accelerating our understanding of the transporters and regulatory networks involved. EDITGENE provides comprehensive services to support researchers in dissecting this function and translating findings into clinical applications.
References
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- 3. Liu X et al.. 2023. Cluster-determinant 36 (CD36) mediates intestinal absorption of dietary astaxanthin and affects its secretion.. Food Res Int 173(Pt 1):113328 PMID: 37803639
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