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 causes increased autophagy at presynaptic terminals, resulting in faster synaptic protein turnover and dopaminergic synapse degeneration. Using a large-s

SUBMITTER: Kilic A 

PROVIDER: S-EPMC12528412 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature