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Updated: Sep 10, 2025
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Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein
Published on: June 16, 2023
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Soma-localized Rab39 inhibits synaptic autophagy by controlling trafficking of Atg9 vesicles
Ayse Kilic1,2, Gokhan Ozturan1,2, Dirk Vandekerkhove1,2
1VIB-KU Leuven Center for Brain & Disease Research, Leuven, 3000, Belgium.
The EMBO Journal
|August 21, 2025
Summary
A soma-centered mechanism regulates synaptic autophagy. Rab39 in the cell body controls protein turnover at distant presynaptic terminals, impacting neuroprotection and Parkinson
Area of Science:
- Neurobiology
- Cell Biology
- Molecular Neuroscience
Background:
- Presynaptic terminals manage their own protein and organelle turnover, crucial for neuronal function.
- Autophagy, a key proteostasis pathway, is vital for synaptic health, and its disruption is linked to neurodegeneration.
Purpose of the Study:
- To investigate a soma-centered mechanism regulating autophagy at distant presynaptic terminals.
- To identify key molecular players in this cross-compartmental regulation.
Main Methods:
- Utilized Drosophila as a model organism.
- Performed a large-scale unbiased genetic modifier screen.
- Investigated the role of Rab39 and its interaction with cytoskeletal proteins.
Main Results:
- Rab39, localized in the soma, regulates synaptic autophagy.
- Loss of Rab39 function or pathogenic mutations increase synaptic autophagy, leading to synapse degeneration.
- Identified Shortstop (Shot) and Unc104/KIF1A as suppressors of synaptic autophagy, mediating Atg9 vesicle delivery.
Conclusions:
- Rab39-mediated somatic trafficking orchestrates synaptic autophagy levels.
- This mechanism highlights a cross-compartmental regulation critical for maintaining synaptic proteostasis.
- Findings implicate Rab39 in neuroprotection and offer insights into Parkinson's disease pathogenesis.
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