GO:0071786 endoplasmic reticulum tubular network organization: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0071786 describes the assembly, arrangement, and disassembly of the endoplasmic reticulum (ER) tubular network, a high-curvature membrane domain distinct from ER sheets.
• The ER tubular network is shaped by curvature-stabilizing proteins and membrane morphogens such as reticulons, DP1/Yop1p, atlastins, and FAM134 family proteins.
• Quantitative proteomics of yeast tubular ER has identified enriched proteins that define the biochemical identity of this compartment.
• Axonal ER tubules are dynamic and their organization is critical for neuronal function; disruption is linked to neurodegeneration.
• Three-dimensional electron microscopy and live-cell imaging remain central methods for studying ER tubular network organization across cell types.
• CRISPR-based knockout, knock-in, and overexpression models enable causal testing of genes implicated in ER tubular network organization.
Description
The endoplasmic reticulum (ER) is a continuous membrane system that includes both sheet-like cisternae and a high-curvature tubular network. GO:0071786, endoplasmic reticulum tubular network organization, refers to the cellular process that assembles, arranges, and disassembles this tubular ER subdomain. This process is essential for diverse functions including lipid synthesis, calcium homeostasis, and the distribution of ER throughout the cell, particularly in highly polarized cells such as neurons. Researchers study GO:0071786 because defects in ER tubule morphogenesis are increasingly associated with neurological disease and because the tubular ER has a distinct protein composition that can be resolved by quantitative proteomics. The tubular ER is not a static structure; it undergoes continuous remodeling driven by curvature-inducing proteins and membrane-shaping mechanisms. Understanding how this network is organized provides insight into basic cell biology and into disease mechanisms where ER architecture is perturbed.
endoplasmic reticulum tubular network organization At A Glance
| GO ID | GO:0071786 |
|---|---|
| GO term | endoplasmic reticulum tubular network organization |
| Ontology | biological_process |
| Synonym | endoplasmic reticulum tubular network organisation; ER tubular network organisation; ER tubular network organization |
| Major function | Assembly, arrangement, and disassembly of the high-curvature tubular ER network |
| Cellular location | Endoplasmic reticulum tubular subdomain |
| Key structural feature | Membranes with high curvature in cross-section |
| Related processes | ER membrane morphogenesis, axonal ER dynamics, ER proteostasis |
What Is GO:0071786?
GO:0071786 is a biological process term defined as the assembly, arrangement of constituent parts, or disassembly of the endoplasmic reticulum tubular network. The ER tubular network is the portion of the ER whose membranes have high curvature in cross-section, distinguishing it from the flat ER sheets. This process occurs at the cellular level and encompasses the dynamic changes that maintain and remodel ER tubules.
Why Is endoplasmic reticulum tubular network organization Important in Cell Biology?
ER tubular network organization is fundamental to cell physiology because the tubular ER provides a large, dynamic membrane surface for lipid synthesis, calcium signaling, and organelle contact sites. Disruption of this process alters ER morphology and has been linked to axonal degeneration and neurodegeneration. The distinct protein composition of tubular ER, revealed by quantitative proteomics, underscores its specialized roles and offers targets for experimental interrogation. Moreover, the biophysical mechanisms that generate and stabilize high-curvature ER tubules are conserved and can be modeled in yeast and mammalian cells.
• Maintains ER architecture required for lipid and calcium homeostasis.
• Supports axonal ER dynamics and neuronal survival.
• Defines a distinct membrane compartment with unique protein composition.
• Involved in ER remodeling during cell division and differentiation.
• Disruption is implicated in hereditary spastic paraplegia and other axonopathies.
• Provides a model for studying membrane curvature generation.
• Relevant to cancer cell biology through altered ER morphology.
• Enables study of ER contact sites and organelle communication.
• Conserved from yeast to humans, facilitating genetic screens.
• Target for CRISPR-based functional genomics of ER-shaping genes.
What Happens During endoplasmic reticulum tubular network organization?
Initiation of ER tubule formation
In simple terms: The cell starts to bend flat ER membranes into tubes.
ER tubule formation begins with the insertion of curvature-inducing proteins into the ER membrane. Proteins such as reticulons and DP1/Yop1p stabilize high membrane curvature, leading to the generation of tubular extensions from the sheet-like ER. In yeast, quantitative proteomics has identified proteins enriched in the tubular ER that participate in this initiation step.
Elongation and stabilization of tubules
In simple terms: The tubes grow longer and are held in shape by proteins.
Once initiated, ER tubules elongate through the action of membrane-shaping proteins and motor-driven sliding along microtubules. Atlastin GTPases promote homotypic fusion between tubules, generating a polygonal network. The tubular network is further stabilized by interactions with the cytoskeleton and by proteins such as FAM134 family members that shape axonal ER architecture in vivo.
Remodeling and disassembly
In simple terms: The tube network is constantly rearranged and can be broken down.
The ER tubular network is dynamic and undergoes continuous remodeling. Disassembly or rearrangement occurs during cell division, stress, and changes in metabolic state. Axonal ER tubules exhibit dynamic movement and can be locally reorganized in response to neuronal activity. The Gp78 ubiquitin ligase has been used as a probe to study ER complexity and may influence tubular network organization.
Three-dimensional organization across cell types
In simple terms: Different cells arrange their ER tubes in distinct patterns.
The three-dimensional organization of the ER tubular network varies by cell type. In renal cell lines MDCK and LLC-PK1, the ER forms distinct tubular arrangements. In ventral photoreceptors of Limulus, the ER tubular network shows specialized geometry. In rat supraoptic neurons, ER organization correlates with structural and functional demands. These studies highlight the diversity of tubular ER architecture.
Key Genes Involved in GO:0071786 endoplasmic reticulum tubular network organization
The following genes and proteins have been experimentally implicated in the organization of the ER tubular network, based on the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FAM134C | Shapes axonal ER architecture | Knockout in mice alters ER tubule morphology |
| FAM134B | Shapes axonal ER architecture | Mutations linked to neuropathy; KO models available |
| RTN4 (Nogo) | Curvature-stabilizing protein | Modulates ER tubule formation |
| RTN3 | Curvature-stabilizing protein | ER tubule morphogenesis |
| DP1/Yop1p | Curvature-stabilizing protein | Yeast tubular ER organization |
| ATL1 (Atlastin-1) | GTPase mediating ER tubule fusion | Hereditary spastic paraplegia |
| ATL2 | ER tubule fusion | ER network formation |
| ATL3 | ER tubule fusion | Sensory neuropathy |
| REEP1 | ER-shaping protein | Hereditary spastic paraplegia |
| REEP2 | ER-shaping protein | Axonal ER organization |
| REEP5 | ER-shaping protein | ER tubule formation |
| LNP (Lunapark) | ER tubule junction protein | ER network stability |
| CLIMP-63 | ER sheet protein | Contrasts with tubular ER |
| SEC61 | ER translocon | Enriched in tubular ER proteome |
| Gp78 (AMFR) | Ubiquitin ligase | Probe for ER complexity |
| Reticulon family | Membrane curvature | General ER tubule shaping |
| Spastin (SPAST) | Microtubule severing | ER tubule remodeling |
How Is endoplasmic reticulum tubular network organization Regulated?
The organization of the ER tubular network is regulated by the availability of curvature-inducing proteins, by GTP-dependent fusion events mediated by atlastins, and by interactions with the cytoskeleton. In neurons, axonal ER dynamics are influenced by neuronal activity and by proteins such as FAM134C and FAM134B. The Gp78 ubiquitin ligase may regulate ER complexity through ubiquitination of ER proteins. Additionally, the tubular ER proteome is dynamically modulated in response to cellular conditions, as shown by quantitative proteomics in yeast.
endoplasmic reticulum tubular network organization and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FAM134B | Hereditary sensory neuropathy | Knockout mouse, patient iPSC-derived neurons |
| ATL1 | Hereditary spastic paraplegia | Knock-in mouse, overexpression in cell lines |
| REEP1 | Hereditary spastic paraplegia | Knockout zebrafish, CRISPR KO in human cells |
| Gp78 (AMFR) | Cancer cell ER remodeling | Overexpression and knockout in cancer cell lines |
| SPAST | Hereditary spastic paraplegia | Knockout mouse, neuronal cultures |
Neurodegeneration and axonopathies
Disruption of ER tubular network organization in axons is increasingly recognized as a contributor to neurodegeneration. FAM134C and FAM134B shape axonal ER architecture in vivo, and their loss alters ER morphology. Axonal ER dynamics are critical for neuronal function, and their perturbation is linked to neurodegenerative diseases.
Hereditary spastic paraplegia
Mutations in ER-shaping proteins such as atlastin-1 and REEP1 cause hereditary spastic paraplegia, a group of axonopathies characterized by degeneration of corticospinal tracts. These proteins are directly involved in ER tubular network organization.
Cancer
Altered ER morphology is a feature of cancer cells, and the Gp78 ubiquitin ligase has been used to probe ER complexity in cancer-related contexts. However, direct links between GO:0071786 and cancer remain an active area of research.
From endoplasmic reticulum tubular network organization-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of FAM134C alter axonal ER tubule density? | FAM134C knockout mouse |
| How does ATL1 mutation affect ER tubule fusion? | ATL1 point-mutation knock-in cell line |
| What proteins are enriched in tubular ER? | Yeast knockout library with quantitative proteomics |
| Does overexpression of reticulons increase ER tubule curvature? | Inducible overexpression in mammalian cells |
| How does Gp78 ubiquitin ligase regulate ER complexity? | Gp78 knockout and overexpression models |
| What is the 3D organization of ER in polarized cells? | 3D electron microscopy of MDCK cells |
How to Study the endoplasmic reticulum tubular network organization Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Quantitative proteomics | Protein composition of tubular ER | Identify enriched proteins in yeast |
| 3D electron microscopy | Three-dimensional ER architecture | Visualize tubular network in cells |
| Live-cell fluorescence imaging | Dynamics of ER tubules | Track axonal ER movement |
| CRISPR knockout screening | Genes required for ER organization | Functional genomics of ER-shaping genes |
| Proximity labeling | Interactome of ER tubule proteins | Map protein networks |
| GTPase assays | Atlastin-mediated fusion | Measure ER tubule fusion activity |
| Membrane curvature sensors | Curvature of ER membranes | Assess tubule formation |
Quantitative proteomics
Quantitative proteomics has been used to identify proteins enriched in the tubular ER of Saccharomyces cerevisiae, providing a biochemical signature of this compartment. This approach can be adapted to mammalian cells to discover novel ER-shaping proteins.
Three-dimensional electron microscopy
Three-dimensional reconstruction of ER in renal cell lines, photoreceptors, and neurons has revealed the complex geometry of the tubular network. These methods are essential for validating morphological changes in CRISPR models.
Live-cell imaging
Live-cell imaging of fluorescently tagged ER proteins allows dynamic tracking of tubule formation, fusion, and disassembly. Axonal ER dynamics have been studied using this approach.
Genetic screens and CRISPR libraries
CRISPR knockout libraries can be used to systematically identify genes required for ER tubular network organization. Yeast deletion collections have already been used in proteomic studies, and mammalian CRISPR screens are applicable to this process.
How CRISPR Can Be Used to Study GO:0071786 endoplasmic reticulum tubular network organization
Knockout
CRISPR knockout of genes such as FAM134C or FAM134B in cell lines or mice can reveal their requirement for ER tubular network organization. For example, knockout of FAM134C alters axonal ER architecture in vivo.
Point Mutation
Point mutations in ATL1 or other ER-shaping genes can be introduced using CRISPR to model hereditary spastic paraplegia and assess effects on ER tubule fusion.
Knock-in
Knock-in of fluorescent tags or disease-associated alleles allows visualization and functional analysis of ER tubular network proteins in their endogenous context.
Overexpression
Overexpression of reticulons or atlastins can drive excessive tubule formation or alter ER morphology, providing gain-of-function models for studying ER tubular network organization.
How EDITGENE Supports endoplasmic reticulum tubular network organization Research
Researchers studying endoplasmic reticulum tubular network organization-related genes often need to determine whether a candidate gene is causally involved in ER morphology, and to dissect the precise domains and residues required for tubule formation. EDITGENE provides end-to-end CRISPR services to generate the necessary cellular and animal models.
Contact EDITGENE today to design your custom CRISPR model for endoplasmic reticulum tubular network organization research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RAB10 Knockout HEK293 Cell Line | EDJ-KQ1881 | Human | 10890 | Details Get a Quote |
| RTN3 Knockout HEK293 Cell Line | EDJ-KQ2281 | Human | 10313 | Details Get a Quote |
| REEP4 Knockout HEK293 Cell Line | EDJ-KQ3229 | Human | 80346 | Details Get a Quote |
| DMTN Knockout HEK293 Cell Line | EDJ-KQ4550 | Human | 2039 | Details Get a Quote |
| TMEM170A Knockout HEK293 Cell Line | EDJ-KQ8569 | Human | 124491 | Details Get a Quote |
| REEP3 Knockout HEK293 Cell Line | EDJ-KQ8791 | Human | 221035 | Details Get a Quote |
| LNPK Knockout HEK293 Cell Line | EDJ-KQ9591 | Human | 80856 | Details Get a Quote |
| REEP2 Knockout HEK293 Cell Line | EDJ-KQ11036 | Human | 51308 | Details Get a Quote |
| RTN4 Knockout HEK293 Cell Line | EDJ-KQ11871 | Human | 57142 | Details Get a Quote |
| REEP1 Knockout HEK293 Cell Line | EDJ-KQ12010 | Human | 65055 | Details Get a Quote |
| RAB18 Knockout HEK293 Cell Line | EDJ-KQ14975 | Human | 22931 | Details Get a Quote |
| RETREG3 Knockout HEK293 Cell Line | EDJ-KQ15038 | Human | 162427 | Details Get a Quote |
| TMEM33 Knockout HEK293 Cell Line | EDJ-KQ15759 | Human | 55161 | Details Get a Quote |
| DMTN Knockout A-549 Cell Line | EDJ-KQ27183 | Human | 2039 | Details Get a Quote |
| DMTN Knockout HCT 116 Cell Line | EDJ-KQ27184 | Human | 2039 | Details Get a Quote |
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Frequently Asked Questions About endoplasmic reticulum tubular network organization
What is GO:0071786?
GO:0071786 is the Gene Ontology term for endoplasmic reticulum tubular network organization, the process that assembles, arranges, and disassembles the high-curvature tubular ER network.
What genes are involved in endoplasmic reticulum tubular network organization?
Key genes include FAM134C, FAM134B, ATL1, REEP1, reticulons, and DP1/Yop1p, as shown in genetic and proteomic studies.
How is the ER tubular network organized?
It is organized by curvature-inducing proteins that generate and stabilize tubules, and by fusion events mediated by atlastin GTPases.
Why is ER tubular network organization important for neurons?
Axonal ER tubules are dynamic and their organization is critical for neuronal function; disruption is linked to neurodegeneration.
What diseases are associated with ER tubular network organization?
Hereditary spastic paraplegia and other axonopathies are associated with mutations in ER-shaping proteins such as ATL1 and REEP1.
What methods are used to study ER tubular network organization?
Quantitative proteomics, 3D electron microscopy, live-cell imaging, and CRISPR screens are commonly used.
Can CRISPR be used to study ER tubular network organization?
Yes, CRISPR knockout, knock-in, and overexpression models enable causal testing of genes involved in this process.
What is the role of FAM134B in ER tubular network organization?
FAM134B shapes axonal ER architecture, and its loss alters ER morphology in vivo.
How does atlastin regulate ER tubule formation?
Atlastin GTPases mediate homotypic fusion of ER tubules, generating a polygonal network.
What is the tubular ER proteome?
It is the set of proteins enriched in the tubular ER, identified by quantitative proteomics in yeast.
Conclusion
GO:0071786 endoplasmic reticulum tubular network organization is a fundamental biological process that shapes a distinct, high-curvature membrane domain of the ER. Research using proteomics, advanced imaging, and CRISPR models has identified key proteins such as FAM134 family members and atlastins that drive this process. Dysregulation of ER tubular network organization is linked to neurodegenerative diseases, making it a compelling area for further study. EDITGENE provides comprehensive CRISPR services to accelerate discoveries in this field.
References
- 1. Iavarone F et al.. 2024. Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo.. EMBO Rep 25(8):3651-3677 PMID: 39039299
- 2. Öztürk Z et al.. 2020. Axonal Endoplasmic Reticulum Dynamics and Its Roles in Neurodegeneration.. Front Neurosci 14:48 PMID: 32116502
- 3. Bergeron M et al.. 1994. Organization of the endoplasmic reticulum in renal cell lines MDCK and LLC-PK1.. Cell Tissue Res 277(2):297-307 PMID: 8082121
- 4. Wang X et al.. 2017. Quantitative proteomics reveal proteins enriched in tubular endoplasmic reticulum of Saccharomyces cerevisiae.. Elife 6 PMID: 28287394
- 5. Zucker B et al.. 2022. Mechanism of shaping membrane nanostructures of endoplasmic reticulum.. Proc Natl Acad Sci U S A 119(1) PMID: 34930828
- 6. Feng JJ et al.. 1994. Three-dimensional organization of endoplasmic reticulum in the ventral photoreceptors of Limulus.. J Comp Neurol 341(2):172-83 PMID: 8163722
- 7. Alonso G et al.. 1979. Three-dimensional organization of the endoplasmic reticulum in supraoptic neurons of the rat. A structural functional correlation.. Brain Res 170(2):247-58 PMID: 466410
- 8. St Pierre P et al.. 2012. The Gp78 ubiquitin ligase: probing endoplasmic reticulum complexity.. Protoplasma 249 Suppl 1:S11-8 PMID: 22045301
