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Updated: Aug 5, 2026

Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Nutrient stress activates RAB5B-mediated autophagy to remodel the synaptic proteome
Melina Overhoff1, Lotte Ickert2, Sebastian Marten1
1Cologne Excellence Cluster for Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Physiology and Pathophysiology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Abstract:
Synaptic proteostasis is crucial for neuronal function, yet how synapses adapt to metabolic stress remains unclear. We show that nutrient stress, particularly serum withdrawal, induces autophagy-dependent remodeling of the synaptic proteome, whereas mTORC1 inhibition produces limited effects. Nutrient stress activates synaptic autophagy within 1-2 h and promotes the recruitment of the LC3 lipidation machinery via RAB5B-positive endosomal compartments in a dynein-dependent manner. Live imaging reveals enhanced RAB5B-ATG16L1 co-trafficking and increased ATG5 mobility upon serum withdrawal, indicating spatiotemporally controlled delivery of autophagy precursors to synaptic compartments. Functionally, nutrient deprivation dampens neuronal activity, while a fasting-mimicking diet induces synaptic proteome remodeling overlapping with starvation-associated autophagy cargo. In contrast, restriction of mTORC1-activating amino acids fails to induce comparable remodeling. Together, these findings identify a RAB5B-mediated trafficking pathway that links nutrient sensing to synaptic degradation, revealing how neurons maintain proteostasis under metabolic challenge.
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