GO:0061764 late endosome to lysosome transport via multivesicular body sorting pathway: Vesicle Trafficking Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061764 describes the directed movement of substances from late endosomes to lysosomes through multivesicular body (MVB) sorting, a conserved route for delivering cargo for degradation.
• The pathway depends on ESCRT complexes that recognize ubiquitinated cargo and drive inward vesicle budding into the endosome, forming the MVB.
• The AAA-ATPase Vps4 and its regulator Ist1 catalyze the final disassembly of ESCRT-III filaments, enabling MVB maturation and lysosomal fusion.
• Defects in MVB sorting are linked to cancer, neurodegeneration, and pathogen interference with membrane trafficking.
• Key experimental approaches include yeast genetics, receptor degradation assays, and CRISPR-based knockout or knock-in models.
• EDITGENE provides CRISPR cell models and library screening to dissect this pathway in disease-relevant contexts.
Description
GO:0061764, late endosome to lysosome transport via multivesicular body sorting pathway, is a biological process that defines how cells deliver membrane proteins and other cargo from late endosomes to lysosomes for degradation. This route requires the sorting of cargo into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs), which then fuse with the lysosome. The pathway is essential for receptor downregulation, nutrient sensing, and cellular quality control, and its dysfunction is associated with cancer and neurological disorders. Researchers study this process to understand how cells maintain proteostasis and how pathogens or mutations hijack or disrupt trafficking. The QuickGO definition emphasizes the directed movement of substances from late endosomes to lysosomes via MVB sorting, distinguishing it from other endosomal trafficking routes.
late endosome to lysosome transport via multivesicular body sorting pathway At A Glance
| GO ID | GO:0061764 |
|---|---|
| GO term | late endosome to lysosome transport via multivesicular body sorting pathway |
| Ontology | biological_process |
| Synonym | none |
| Major function | Sorting of cargo into multivesicular bodies and delivery to lysosomes for degradation |
| Key complexes | ESCRT-0, -I, -II, -III, Vps4 complex |
| Cellular location | Late endosome, multivesicular body, lysosome |
| Associated diseases | Cancer, neurodegeneration, pathogen infections |
What Is GO:0061764?
In our own words, GO:0061764 is the cellular process in which molecules are actively sorted into multivesicular bodies within late endosomes and then transported to lysosomes by fusion, leading to the degradation of the sorted cargo. This definition is based on the QuickGO entry for GO:0061764 and reflects the directed movement of substances from late endosomes to lysosomes via MVB sorting.
Why Is late endosome to lysosome transport via multivesicular body sorting pathway Important in Cell Biology?
This pathway is critical for controlling the abundance of cell surface receptors, such as the EGF receptor, and for degrading damaged proteins, thereby influencing cell signaling, growth, and survival. Its impairment can lead to aberrant signaling, accumulation of toxic aggregates, and increased susceptibility to infections, making it a focal point for research in cancer biology, neurobiology, and infectious disease.
• Regulates downregulation of growth factor receptors like EGFR, affecting cancer progression.
• Maintains neuronal health by clearing aggregated proteins; defects are linked to neurodegeneration.
• Mediates pathogen interference, as some bacterial effectors disrupt MVB sorting.
• Controls nutrient sensing and membrane protein turnover.
• Provides a model for studying ubiquitin-dependent sorting mechanisms.
• Involves conserved ESCRT machinery that is essential for cell division and viral budding.
• Offers targets for therapeutic intervention in diseases with trafficking defects.
• Enables investigation of basic cell biology through yeast genetics.
What Happens During late endosome to lysosome transport via multivesicular body sorting pathway?
Cargo Recognition and Sorting at the Late Endosome
In simple terms: The cell tags certain proteins with ubiquitin so they can be recognized and sorted into late endosomes.
Cargo proteins destined for degradation are modified with ubiquitin and recognized by ESCRT-0 and ESCRT-I complexes at the late endosomal membrane. This recognition ensures that only specific cargo is incorporated into the MVB pathway, while other proteins are recycled.
Formation of Intraluminal Vesicles and Multivesicular Bodies
In simple terms: The late endosome membrane buds inward to form small vesicles inside, creating a multivesicular body.
ESCRT-I and ESCRT-II recruit ESCRT-III, which drives inward budding of the endosomal membrane to form intraluminal vesicles (ILVs). The coordinated action of these complexes leads to the formation of multivesicular bodies (MVBs), which contain the sorted cargo within their lumen.
ESCRT-III Disassembly and MVB Maturation
In simple terms: A molecular machine called Vps4 takes apart the ESCRT-III filaments so the multivesicular body can mature.
The AAA-ATPase Vps4, regulated by Ist1, disassembles ESCRT-III filaments, allowing the MVB to complete its formation and detach from the endosomal membrane. This step is essential for the subsequent fusion of MVBs with lysosomes.
Fusion of Multivesicular Bodies with Lysosomes
In simple terms: The multivesicular body fuses with the lysosome, delivering its contents for degradation.
After maturation, MVBs fuse with lysosomes, a process that requires Rab GTPases and SNARE proteins. The cargo is then degraded by lysosomal hydrolases, completing the transport pathway defined by GO:0061764.
Key Genes Involved in GO:0061764 late endosome to lysosome transport via multivesicular body sorting pathway
The following genes and proteins are central to the late endosome to lysosome transport via multivesicular body sorting pathway, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| TSG101 | ESCRT-I component that recognizes ubiquitinated cargo | Knockout studies reveal defects in receptor degradation |
| VPS4 | AAA-ATPase that disassembles ESCRT-III filaments | Dominant-negative mutants block MVB sorting |
| IST1 | Regulates Vps4 localization and assembly | Knockdown affects ESCRT-III disassembly |
| SH3YL1 | Cooperates with ESCRT-I in EGFR sorting | Overexpression enhances EGFR degradation |
| VPS23 | Yeast ESCRT-I component | Used in yeast genetics to study sorting |
| VPS27 | ESCRT-0 component in yeast | Deletion causes cargo missorting |
| VPS36 | ESCRT-II component | Essential for ILV formation |
| SNF7 | ESCRT-III subunit | Mutations impair MVB sorting |
| VPS20 | ESCRT-III subunit | Required for ESCRT-III assembly |
| DID2 | Yeast Ist1 homolog | Regulates Vps4 activity |
| VPS28 | ESCRT-I component | Involved in ubiquitin recognition |
| VPS37 | ESCRT-I component | Part of the ESCRT-I complex |
| MVB12 | ESCRT-I associated protein | Modulates EGFR sorting |
| RAB7 | Late endosomal GTPase | Required for MVB fusion with lysosome |
| VPS25 | ESCRT-II subunit | Mutations affect MVB formation |
| VPS32 | ESCRT-III subunit | Essential for membrane scission |
| CHMP4B | Human ESCRT-III protein | Involved in MVB sorting |
How Is late endosome to lysosome transport via multivesicular body sorting pathway Regulated?
The pathway is regulated by ubiquitination of cargo and the activity of ESCRT complexes, which are controlled by phosphorylation and interactions with accessory proteins such as Ist1. Vps4 activity is critical for recycling ESCRT components, and its regulation ensures proper MVB sorting. Additionally, pathogen effectors can interfere with this pathway, as shown by Legionella factors that disrupt membrane trafficking.
late endosome to lysosome transport via multivesicular body sorting pathway and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TSG101 | Cancer, viral budding | Knockout cell lines for receptor degradation assays |
| VPS4 | Neurodegeneration, cancer | Dominant-negative overexpression models |
| SH3YL1 | EGFR-related cancers | Knockdown and overexpression in cancer cells |
| IST1 | Trafficking disorders | CRISPR knockout in neuronal cells |
| RAB7 | Charcot-Marie-Tooth disease | Knock-in of disease mutations |
Cancer
Dysregulation of MVB sorting leads to accumulation of growth factor receptors like EGFR, promoting uncontrolled cell proliferation. ESCRT components are often altered in cancers, making this pathway a target for therapeutic intervention.
Neurodegeneration
Impaired MVB sorting contributes to the accumulation of toxic protein aggregates in neurons, a hallmark of neurodegenerative diseases. Proper functioning of this pathway is essential for neuronal survival.
Infectious Diseases
Pathogens such as Legionella secrete effectors that interfere with MVB sorting to evade host defenses. Understanding these interactions can inform new antimicrobial strategies.
From late endosome to lysosome transport via multivesicular body sorting pathway-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate MVB sorting? | CRISPR knockout cell lines |
| How does a point mutation affect ESCRT function? | Point mutation knock-in models |
| Where does protein X localize during MVB sorting? | Tagged knock-in with fluorescent tags |
| Does overexpression of gene Y enhance EGFR degradation? | Overexpression cell lines |
| Which genes are essential for MVB sorting? | CRISPR library screening |
| How does pathogen effector Z interfere with trafficking? | Yeast pathogen effector screening |
How to Study the late endosome to lysosome transport via multivesicular body sorting pathway Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Yeast vacuolar sorting assay | Sorting of CPY to vacuole | Identification of VPS genes |
| EGFR degradation assay | Receptor downregulation | ESCRT function in cancer cells |
| Fluorescence microscopy | MVB and lysosome localization | Visualizing trafficking defects |
| Co-immunoprecipitation | Protein-protein interactions | ESCRT complex assembly |
| CRISPR knockout | Gene function loss | Studying essential MVB genes |
| RNA interference | Gene knockdown | Transient inhibition of sorting |
| Proteomics | Cargo identification | Ubiquitin-dependent sorting |
| Pathogen effector screening | Interference with trafficking | Host-pathogen interactions |
Genetic Screens in Yeast
Yeast genetics has been instrumental in identifying MVB sorting components, such as VPS genes, through screens for vacuolar protein sorting defects. These screens use reporter proteins to assess sorting efficiency.
Receptor Degradation Assays
EGFR degradation assays measure the efficiency of MVB sorting by tracking receptor levels after ligand stimulation. This method is widely used to study ESCRT function.
Imaging of MVB and Lysosome Fusion
Fluorescence microscopy and live-cell imaging visualize MVB formation and fusion with lysosomes, often using tagged markers like GFP-Rab7.
Proteomics and Ubiquitin Profiling
Mass spectrometry-based proteomics identifies cargo and ESCRT interactors, while ubiquitin profiling reveals sorting signals.
How CRISPR Can Be Used to Study GO:0061764 late endosome to lysosome transport via multivesicular body sorting pathway
Knockout
CRISPR knockout of ESCRT genes such as TSG101 or VPS4 abolishes MVB sorting, leading to accumulation of cargo on late endosomes. These models are used to study the consequences of pathway loss in cancer and neurodegeneration.
Point Mutation
Point mutations in genes like VPS4 can mimic disease-associated variants, allowing researchers to dissect subtle effects on ATPase activity and ESCRT disassembly.
Knock-in
Knock-in of tagged proteins, such as GFP-Rab7, enables real-time visualization of MVB dynamics and lysosomal fusion in live cells.
Overexpression
Overexpression of SH3YL1 or other ESCRT components can enhance or disrupt sorting, providing gain-of-function models to study pathway regulation.
How EDITGENE Supports late endosome to lysosome transport via multivesicular body sorting pathway Research
Researchers studying late endosome to lysosome transport via multivesicular body sorting pathway-related genes often need to determine whether a candidate gene is causally involved in cargo sorting, MVB formation, or lysosomal delivery. EDITGENE provides the CRISPR tools and cell models to answer these questions with precision.
Contact EDITGENE today to design your custom CRISPR model for late endosome to lysosome transport via multivesicular body sorting pathway research.
Frequently Asked Questions About late endosome to lysosome transport via multivesicular body sorting pathway
What is GO:0061764?
GO:0061764 is the Gene Ontology term for late endosome to lysosome transport via multivesicular body sorting pathway, a process where cargo is sorted into MVBs and delivered to lysosomes for degradation.
What genes are involved in late endosome to lysosome transport via multivesicular body sorting pathway?
Key genes include TSG101, VPS4, IST1, SH3YL1, and RAB7, among others.
How does the ESCRT machinery function in MVB sorting?
ESCRT complexes recognize ubiquitinated cargo and drive inward vesicle budding, with Vps4 disassembling ESCRT-III to complete MVB formation.
What diseases are associated with defects in MVB sorting?
Defects are linked to cancer, neurodegeneration, and infectious diseases.
What methods are used to study this pathway?
Common methods include yeast genetics, EGFR degradation assays, fluorescence microscopy, and CRISPR screens.
What is the role of Vps4 in MVB sorting?
Vps4 is an AAA-ATPase that disassembles ESCRT-III filaments, enabling MVB maturation and lysosomal fusion.
How can CRISPR be used to study MVB sorting?
CRISPR knockout, knock-in, and overexpression models allow functional dissection of genes in this pathway.
What is the difference between MVB sorting and other endosomal pathways?
MVB sorting specifically routes cargo into intraluminal vesicles for lysosomal degradation, unlike recycling pathways.
Which model organisms are used to study GO:0061764?
Yeast is a powerful model due to conserved VPS genes and tractable genetics.
How does pathogen infection affect MVB sorting?
Some pathogens secrete effectors that interfere with MVB sorting to evade host immunity.
Conclusion
GO:0061764 represents a fundamental cellular pathway for protein degradation and signaling regulation, with broad implications for human health and disease. Understanding its molecular players and regulatory mechanisms offers opportunities for therapeutic intervention. EDITGENE's CRISPR services empower researchers to dissect this pathway with precision and scale.
References
- 1. Toshima J et al.. 2026. Endocytosis and trans-Golgi Network in Yeast.. Subcell Biochem 110:335-358 PMID: 41240318
- 2. Bishop NE. 2003. Dynamics of endosomal sorting.. Int Rev Cytol 232:1-57 PMID: 14711115
- 3. Robinson DG et al.. 2016. Receptor-mediated sorting of soluble vacuolar proteins: myths, facts, and a new model.. J Exp Bot 67(15):4435-49 PMID: 27262127
- 4. Dimaano C et al.. 2008. Ist1 regulates Vps4 localization and assembly.. Mol Biol Cell 19(2):465-74 PMID: 18032582
- 5. Hasegawa J et al.. 2019. SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor.. J Cell Sci 132(19) PMID: 31492760
- 6. Sundquist WI et al.. 2004. Ubiquitin recognition by the human TSG101 protein.. Mol Cell 13(6):783-9 PMID: 15053872
- 7. Chen L et al.. 2002. Ubiquitin-independent entry into the yeast recycling pathway.. Traffic 3(2):110-23 PMID: 11929601
- 8. Shohdy N et al.. 2005. Pathogen effector protein screening in yeast identifies Legionella factors that interfere with membrane trafficking.. Proc Natl Acad Sci U S A 102(13):4866-71 PMID: 15781869
