Soma-localized Rab39 inhibits synaptic autophagy by controlling trafficking of Atg9 vesicles

ABSTRACT: Presynaptic terminals can be located far from the neuronal cell body and are thought to independently regulate protein and organelle turnover. Autophagy is a critical process for maintaining proteostasis, and its synaptic dysregulation is associated with neurodegenerative diseases. In this work, we report a soma-centered mechanism that regulates autophagy-controlled protein turnover at distant presynaptic terminals in Drosophila. We show that a central component of this system is Rab39, whose human homolog RAB39B is mutated in Parkinson's disease. Although Rab39 is localized in the soma, its loss of function or a human pathogenic mutation cause increased autophagy at presynaptic terminals, resulting in faster synaptic protein turnover and dopaminergic synapse degeneration. Using a large-sc

SUBMITTER: Ayse Kilic 

PROVIDER: S-SCDT-10_1038-S44318-025-00536-8 | biostudies-other |

REPOSITORIES: biostudies-other