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Updated: Jun 5, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
Rubicon regulates exosome secretion via the non-autophagic pathway
Kyosuke Yanagawa1,2, Tamotsu Yoshimori1,3,4
1Department of Genetics, Graduate School of Medicine, Osaka University, Suita, Japan.
Abstract:
Exosomes are small extracellular vesicles (EVs), which have the diameter of 50-150 nm and originate from intralumenal vesicles in multivesicular endosomes (MVBs). Exosomes secreted from donor cells are delivered to recipient cells for transferring of exosome cargos, such as proteins, lipids and nucleic acids. The cargo transfer by exosomes has a pivotal role in cell-to-cell communication for many cellular processes; however, the detailed mechanism remains largely elusive. In our recent study, we found that RUBCN/rubicon regulates exosome secretion through endosomal recruitment of WIPI2, which promotes ESCRT-dependent MVB formation. We further showed that this pathway is essential for age-dependent increasing of exosomes, which transfer the pro-senescent microRNAs, including Mir26a and Mir486a, and accelerate cellular senescence in the recipient cells. Our findings highlight RUBCN's key role in exosome secretion and its impact on cellular senescence, providing insights into its potential contributions to aging.
Insights
Rubicon (RUBCN) regulates exosome secretion, promoting cellular senescence. This pathway is crucial for age-related increases in exosomes carrying pro-senescent microRNAs, impacting recipient cells.
Area of Science:
- Cell Biology
- Extracellular Vesicles
- Aging Research
Background:
- Exosomes, small extracellular vesicles (EVs), mediate cell-to-cell communication via cargo transfer.
- The precise mechanisms regulating exosome secretion and their role in aging are not fully understood.
Purpose of the Study:
- To elucidate the role of RUBCN/rubicon in exosome secretion.
- To investigate the link between RUBCN-mediated exosome secretion and cellular senescence.
Main Methods:
- Investigated the interaction of RUBCN with WIPI2 in endosomal pathways.
- Analyzed the impact of RUBCN on ESCRT-dependent multivesicular body (MVB) formation.
- Quantified exosome secretion and microRNA content in aging cells.
Main Results:
- RUBCN regulates exosome secretion by recruiting WIPI2, promoting ESCRT-dependent MVB formation.
- This pathway is essential for the age-dependent increase in exosome secretion.
- These exosomes carry pro-senescent microRNAs (e.g., Mir26a, Mir486a) that accelerate senescence in recipient cells.
Conclusions:
- RUBCN plays a critical role in regulating exosome secretion.
- The RUBCN pathway contributes to age-related cellular senescence through exosome-mediated microRNA transfer.
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