Related Experiment Video
Updated: Sep 6, 2025

06:58
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
801
TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
Tao Zhang1, Lili Zhao1, Liping Han1
1College of Life Sciences, Sichuan University, Chengdu 610065, China.
International Journal of Molecular Sciences
|June 24, 2022
Summary
Mitochondrial thioredoxin 2 (TRX2) inhibits exosome secretion and cell migration by degrading Rab35. This study reveals TRX2
Area of Science:
- Cell Biology
- Molecular Biology
- Cancer Research
Background:
- Exosomes mediate intercellular communication and hold therapeutic potential.
- Mechanisms regulating exosome secretion are not fully understood.
- Mitochondrial components in exosomes suggest mitochondria-vesicle communication.
Purpose of the Study:
- Investigate the role of mitochondrial thioredoxin 2 (TRX2) in exosome secretion.
- Elucidate the molecular mechanism linking mitochondria and exosome release.
- Determine the impact of TRX2 on cell migration.
Main Methods:
- Coimmunoprecipitation/mass spectrometry (Co-IP/MS) to identify protein interactions.
- Analysis of exosome concentration and cell migration assays.
- Investigation of protein localization and degradation pathways.
Main Results:
- Mitochondrial TRX2 interacts with Rab35.
- TRX2 induces Rab35 degradation, impairing exosome secretion.
- TRX2 suppresses HCT116 cell migration, mediated by Rab35 and exosomes.
Conclusions:
- TRX2 plays a novel regulatory role in exosome secretion and cell migration.
- TRX2-Rab35 interaction provides insight into upstream regulation of Rab35.
- Findings offer molecular evidence for mitochondria-vesicle communication.
Related Concept Videos
Rab Cascades
2.7K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.7K
Rab Proteins
4.1K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.1K
Recycling Endosomes and Transcytosis
2.8K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.8K
mRNA Stability and Gene Expression
5.7K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.7K
Export of Misfolded Proteins out of the ER
3.9K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.9K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K

