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Updated: Aug 6, 2026
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
TBC1D9 and TBC1D9B are ARL8 effectors that modulate exosome secretion through a RAB11A-exocyst pathway
Ganesh Vilas Shelke1, Chad D Williamson1, Tal Keren-Kaplan1
1Division of Neuroscience and Cellular Structure, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Summary
Researchers identified a new pathway involving BORC, ARL8, and TBC1D9/TBC1D9B proteins that suppresses the release of exosomes. This discovery helps explain how multivesicular endosomes decide whether to degrade their contents or secrete them as exosomes.
Area of Science:
- Cell Biology
- Molecular Biology
- Endosomal Sorting
Background:
- Multivesicular endosomes (MVEs) traffic intraluminal vesicles (ILVs) via lysosomal degradation or plasma membrane secretion as exosomes.
- The Biogenesis of lysosome related organelles complex-one-related complex (BORC) and ARL8 GTPase promote MVE-lysosome fusion, inhibiting exosome release.
Purpose of the Study:
- To elucidate the molecular mechanisms governing MVE fate decisions.
- To identify novel regulators of exosome secretion.
Main Methods:
- Investigated the role of TBC1D9 and TBC1D9B as ARL8 effectors.
- Analyzed the impact of these proteins on RAB11A inactivation and exocyst complex recruitment.
Main Results:
- TBC1D9 and TBC1D9B function as GTPase-activating proteins for RAB11A, promoting its inactivation and dissociation from endolysosomes.
- This action reduces the recruitment of the exocyst complex, thereby inhibiting MVE fusion with the plasma membrane and suppressing exosome secretion.
Conclusions:
- A BORC-ARL8-TBC1D9/TBC1D9B signaling axis was defined.
- This axis further suppresses exosome secretion by blocking MVE-plasma membrane fusion, providing new insights into exosome biogenesis regulation.
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