GO:0097320 plasma membrane tubulation: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0097320 plasma membrane tubulation is the biological process by which the plasma membrane is shaped into tubular invaginations or protrusions.
• Microtubule motors and their associated forces can power plasma membrane tubulation during clathrin-independent endocytosis.
• Phosphatidic acid and diacylglycerol are lipid signals that accumulate at curved membrane regions and promote tubulation.
• LRRK2 mediates tubulation and vesicle sorting from lysosomes, linking membrane tubulation to Parkinson's disease biology.
• TECPR1-mediated membrane tubulation repairs damaged lysosomes during energy crisis, showing tubulation is a stress-response mechanism.
• Pathogens such as meningococci can drive host membrane tubulation to recruit signaling receptors, highlighting its role in infection.
Description
Plasma membrane tubulation (GO:0097320) is a fundamental cellular process in which the plasma membrane is remodeled into tubular structures. This process is distinct from other membrane deformation events because it specifically occurs at the plasma membrane and generates elongated, curved membrane tubes rather than spherical vesicles. Plasma membrane tubulation is essential for diverse functions including endocytosis, vesicle trafficking, and cellular signaling, and it is driven by coordinated actions of proteins, lipids, and cytoskeletal forces. Understanding this process is critical because defects in membrane tubulation are linked to human diseases such as Parkinson's disease and infections. Moreover, membrane tubulation is a key mechanism for repairing damaged organelles and maintaining cellular homeostasis under stress. Researchers study plasma membrane tubulation to uncover how cells control membrane shape and how this control goes awry in disease. The process also serves as a model for understanding fundamental principles of membrane curvature generation and sensing. As such, GO:0097320 represents a convergence point for cell biology, neuroscience, and infectious disease research.
plasma membrane tubulation At A Glance
| GO ID | GO:0097320 |
|---|---|
| GO term | plasma membrane tubulation |
| Ontology | biological_process |
| Synonym | membrane tubulation, vesicle scission |
| Major function | Generation of tubular membrane structures from the plasma membrane for endocytosis, trafficking, and signaling |
| Cellular location | Plasma membrane |
| Related processes | Clathrin-independent endocytosis, lysosomal tubulation, membrane repair |
What Is GO:0097320?
According to the Gene Ontology, plasma membrane tubulation (GO:0097320) is defined as a membrane tubulation process occurring in a plasma membrane. In other words, it is the cellular process that generates tubular extensions or invaginations from the plasma membrane, often involving membrane curvature and remodeling. This process is synonymous with membrane tubulation and is sometimes associated with vesicle scission events at the plasma membrane.
Why Is plasma membrane tubulation Important in Cell Biology?
Plasma membrane tubulation is important because it underlies essential cellular activities such as endocytosis, vesicle sorting, and membrane repair, and its dysregulation is implicated in diseases ranging from Parkinson's disease to bacterial infections. The process also represents a key mechanism by which cells respond to stress, as seen in lysosomal repair during energy crisis. Understanding plasma membrane tubulation provides insights into fundamental membrane biology and offers potential therapeutic targets for diseases where membrane trafficking is disrupted.
• Enables clathrin-independent endocytosis and cargo uptake.
• Facilitates vesicle sorting from lysosomes and other organelles.
• Mediates repair of damaged lysosomes during energy stress.
• Is exploited by pathogens like meningococci to recruit host receptors.
• Involves lipid signals such as phosphatidic acid and diacylglycerol that sense curvature.
• Linked to Parkinson's disease through LRRK2-mediated tubulation.
• Contributes to outer retinal tubulation in macular telangiectasia type 2.
• Regulated by membrane tension and trafficking pathways.
• Provides a model for studying membrane curvature generation.
• Potential target for anti-infective and neuroprotective therapies.
What Happens During plasma membrane tubulation?
Initiation and membrane curvature generation
In simple terms: The plasma membrane starts to bend inward or outward to form a tube.
Plasma membrane tubulation begins with the generation of membrane curvature, often triggered by lipid composition changes or protein recruitment. Phosphatidic acid accumulates at areas of curvature in tubulated lipid bilayers, suggesting that specific lipids promote and stabilize tubular shapes. Similarly, acute diacylglycerol production activates critical membrane-shaping proteins that lead to mitochondrial tubulation and fission, indicating that lipid signals are conserved drivers of tubulation. These lipid-mediated events create the initial curvature necessary for tube formation.
Force generation by microtubule motors
In simple terms: Molecular motors pull on the membrane to extend tubes.
Microtubule motors power plasma membrane tubulation during clathrin-independent endocytosis, as shown by Day et al. (2015). These motors generate mechanical forces that pull the plasma membrane into tubular invaginations, which are then used for cargo uptake. This force-dependent mechanism highlights the interplay between the cytoskeleton and membrane remodeling in tubulation.
Vesicle sorting and scission
In simple terms: The tube pinches off to release vesicles.
Once a tubule is formed, it can undergo scission to release vesicles. LRRK2 mediates tubulation and vesicle sorting from lysosomes, demonstrating that tubulation is coupled to cargo sorting and vesicle formation. This step is critical for directing specific proteins and lipids to their destinations, and defects can lead to disease.
Membrane repair and stress response
In simple terms: Cells use tubulation to fix damaged membranes.
TECPR1-mediated membrane tubulation repairs damaged lysosomes during energy crisis, indicating that tubulation is a stress-responsive repair mechanism. This process helps maintain organelle integrity under conditions of energy deprivation, linking plasma membrane tubulation to cellular survival pathways.
Pathogen-driven tubulation
In simple terms: Some bacteria hijack tubulation to infect cells.
Meningococci drive host membrane tubulation to recruit their signaling receptors, as reported by Laurent-Granger et al. (2025). This example illustrates how pathogens exploit plasma membrane tubulation for their own entry and signaling, making it a target for anti-infective strategies.
Key Genes Involved in GO:0097320 plasma membrane tubulation
The following genes and proteins are key players in plasma membrane tubulation, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| LRRK2 | Mediates tubulation and vesicle sorting from lysosomes | Linked to Parkinson's disease; target for neurodegeneration studies |
| TECPR1 | Mediates membrane tubulation for lysosome repair | Role in energy crisis and lysosomal damage response |
| DNM2 | Dynamin 2, involved in membrane scission | Potential role in tubulation and endocytosis |
| CLTC | Clathrin heavy chain, involved in endocytosis | May interact with tubulation pathways |
| PLD1 | Phospholipase D1, produces phosphatidic acid | Phosphatidic acid accumulates at curved membranes |
| DGK | Diacylglycerol kinase, regulates diacylglycerol | Diacylglycerol production activates membrane-shaping proteins |
| KIF5B | Kinesin motor, generates force on microtubules | Microtubule motors power plasma membrane tubulation |
| DYNC1H1 | Dynein motor, generates force on microtubules | Potential role in tubulation force generation |
| RAB7 | Late endosomal GTPase | Involved in lysosomal tubulation and sorting |
| VPS35 | Retromer component | May interact with LRRK2-mediated tubulation |
| ATP13A2 | Lysosomal ATPase | Linked to Parkinson's disease and lysosomal function |
| SNX1 | Sorting nexin, membrane curvature sensor | Potential role in tubulation and sorting |
| BIN1 | Membrane curvature protein | Implicated in membrane remodeling |
| EHD2 | Membrane tubulation and curvature protein | Involved in plasma membrane dynamics |
| CAV1 | Caveolin-1, forms caveolae | Caveolae are related to membrane tubulation |
| ACAP1 | ArfGAP with coiled-coil domain | Potential role in membrane trafficking |
| MTM1 | Myotubularin, lipid phosphatase | Regulates phosphoinositides in membrane tubulation |
How Is plasma membrane tubulation Regulated?
Plasma membrane tubulation is regulated by membrane tension and trafficking pathways, as reviewed by Saric et al. (2020). Changes in endomembrane tension can influence the formation and stability of membrane tubes. Additionally, lipid-modifying enzymes such as phospholipase D and diacylglycerol kinase regulate the availability of phosphatidic acid and diacylglycerol, which in turn control membrane curvature and tubulation. Protein kinases like LRRK2 also play a regulatory role by mediating tubulation and vesicle sorting.
plasma membrane tubulation and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| LRRK2 | Parkinson's disease | Knockout or point-mutation iPSC-derived neurons |
| TECPR1 | Lysosomal damage response | Knockout HeLa cells under energy stress |
| Meningococcal factors | Bacterial infection | Host cell knockouts of receptor genes |
| MTM1 | Myotubular myopathy | Knockout muscle cells |
| BIN1 | Neurodegeneration | Knock-in mouse models |
Parkinson's disease and neurodegeneration
LRRK2-mediated tubulation and vesicle sorting from lysosomes is linked to Parkinson's disease, as mutations in LRRK2 are a common genetic cause of the disorder. Defects in this process may contribute to lysosomal dysfunction and neuronal death. Understanding how LRRK2 regulates plasma membrane tubulation could lead to new therapeutic strategies.
Infectious diseases
Meningococci drive host membrane tubulation to recruit their signaling receptors, highlighting a role for plasma membrane tubulation in bacterial pathogenesis. This mechanism allows pathogens to manipulate host cell signaling and may be targeted for anti-infective therapies.
Retinal diseases
Outer retinal tubulation in subretinal neovascularization associated with macular telangiectasia type 2 suggests that tubulation processes occur in retinal pathology. Although this is a different context, it underscores the broader relevance of membrane tubulation in disease.
Lysosomal storage and energy stress
TECPR1-mediated membrane tubulation repairs damaged lysosomes during energy crisis, linking tubulation to cellular stress responses. Defects in this pathway could contribute to lysosomal storage disorders and neurodegeneration.
From plasma membrane tubulation-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does LRRK2 kinase activity regulate tubulation? | Point mutation (kinase-dead) knock-in |
| What is the role of TECPR1 in lysosome repair? | Knockout cell line |
| How does phosphatidic acid affect tubulation? | Overexpression of PLD1 |
| Does diacylglycerol signaling control tubulation? | Knockout of DGK |
| Can pathogens recruit receptors via tubulation? | Knockout of host receptor |
| What is the effect of membrane tension on tubulation? | Tagged knock-in of mechanosensitive proteins |
How to Study the plasma membrane tubulation Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Tubulation dynamics | Visualizing tube formation in real time |
| Lipidomics | Phosphatidic acid and diacylglycerol levels | Linking lipid signals to curvature |
| Proteomics | Protein interactions | Identifying tubulation machinery |
| CRISPR screen | Gene essentiality | Discovering new tubulation regulators |
| Electron microscopy | Ultrastructure of tubules | High-resolution imaging of membrane tubes |
| Membrane tension assays | Tension changes | Studying mechanical regulation |
| Bacterial infection assays | Pathogen-driven tubulation | Host-pathogen interaction studies |
Live-cell imaging
Live-cell fluorescence microscopy allows real-time visualization of plasma membrane tubulation dynamics. Tagged proteins such as LRRK2 or TECPR1 can be tracked to observe tube formation and scission.
Lipid analysis
Mass spectrometry-based lipidomics can quantify phosphatidic acid and diacylglycerol levels during tubulation. This helps link lipid signals to membrane curvature.
Proteomics
Proteomic approaches identify proteins enriched in tubulated membranes. For example, immunoprecipitation of LRRK2 followed by mass spectrometry reveals interacting partners.
Genetic screens
CRISPR knockout screens can identify genes required for plasma membrane tubulation. Such screens have uncovered factors like TECPR1 and LRRK2.
How CRISPR Can Be Used to Study GO:0097320 plasma membrane tubulation
Knockout
CRISPR knockout of genes like LRRK2 or TECPR1 can abolish plasma membrane tubulation, revealing their essential roles. For example, TECPR1 knockout impairs lysosome repair during energy crisis.
Point Mutation
Point mutations in LRRK2, such as kinase-dead variants, can dissect the role of its enzymatic activity in tubulation. This approach helps distinguish between scaffolding and catalytic functions.
Knock-in
Knock-in of tagged proteins, such as GFP-LRRK2, allows visualization of tubulation in live cells. This enables tracking of dynamic membrane remodeling.
Overexpression
Overexpression of phospholipase D1 or diacylglycerol kinase can increase phosphatidic acid or diacylglycerol levels, respectively, enhancing tubulation. This helps test sufficiency of lipid signals.
How EDITGENE Supports plasma membrane tubulation Research
Researchers studying plasma membrane tubulation-related genes often need to determine whether a candidate gene is causally involved in the process or is merely correlated. EDITGENE provides CRISPR-based services to enable such functional studies with high precision.
Contact EDITGENE today to design your custom CRISPR model for plasma membrane tubulation research.
Frequently Asked Questions About plasma membrane tubulation
What is plasma membrane tubulation?
Plasma membrane tubulation (GO:0097320) is the process by which the plasma membrane is shaped into tubular structures, often for endocytosis, vesicle sorting, or membrane repair.
What genes are involved in plasma membrane tubulation?
Key genes include LRRK2, TECPR1, PLD1, DGK, and microtubule motors such as KIF5B.
How is plasma membrane tubulation regulated?
It is regulated by membrane tension, lipid signals like phosphatidic acid and diacylglycerol, and protein kinases such as LRRK2.
What diseases are linked to plasma membrane tubulation?
Parkinson's disease, bacterial infections, and retinal diseases have been associated with tubulation defects.
What is the role of LRRK2 in plasma membrane tubulation?
LRRK2 mediates tubulation and vesicle sorting from lysosomes, and mutations in LRRK2 are linked to Parkinson's disease.
How can I study plasma membrane tubulation in the lab?
Live-cell imaging, lipidomics, proteomics, and CRISPR screens are common methods.
What is TECPR1 and how does it relate to tubulation?
TECPR1 mediates membrane tubulation to repair damaged lysosomes during energy crisis.
Can pathogens exploit plasma membrane tubulation?
Yes, meningococci drive host membrane tubulation to recruit their signaling receptors.
What is the difference between plasma membrane tubulation and vesicle scission?
Tubulation is the formation of membrane tubes, while vesicle scission is the pinching off of vesicles from these tubes.
What CRISPR models are available for tubulation research?
Knockout, point mutation, knock-in, and overexpression models can be generated for genes like LRRK2 and TECPR1.
Conclusion
Plasma membrane tubulation (GO:0097320) is a critical cellular process that shapes the plasma membrane into tubes for diverse functions including endocytosis, vesicle sorting, and membrane repair. Its dysregulation is linked to Parkinson's disease, infections, and retinal pathologies. Studying this process using CRISPR-based models and advanced imaging will continue to reveal new mechanistic insights and therapeutic opportunities.
References
- 1. Chen H et al.. 2026. Repair of damaged lysosomes by TECPR1-mediated membrane tubulation during energy crisis.. Cell Res 36(1):51-71 PMID: 41478856
- 2. Bonet-Ponce L et al.. 2020. LRRK2 mediates tubulation and vesicle sorting from lysosomes.. Sci Adv 6(46) PMID: 33177079
- 3. Hua DA et al.. 2018. Outer Retinal Tubulation in Subretinal Neovascularization Associated with Macular Telangiectasia Type 2.. Semin Ophthalmol 33(3):331-337 PMID: 27960639
- 4. Bills BL et al.. 2022. Phosphatidic Acid Accumulates at Areas of Curvature in Tubulated Lipid Bilayers and Liposomes.. Biomolecules 12(11) PMID: 36421720
- 5. Day CA et al.. 2015. Microtubule motors power plasma membrane tubulation in clathrin-independent endocytosis.. Traffic 16(6):572-90 PMID: 25690058
- 6. Pemberton JG et al.. 2025. Acute diacylglycerol production activates critical membrane-shaping proteins leading to mitochondrial tubulation and fission.. Nat Commun 16(1):2685 PMID: 40102394
- 7. Laurent-Granger A et al.. 2025. Meningococci drive host membrane tubulation to recruit their signaling receptors.. Nat Commun 16(1):10433 PMID: 41290585
- 8. Saric A et al.. 2020. Endomembrane Tension and Trafficking.. Front Cell Dev Biol 8:611326 PMID: 33490077
