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Updated: Sep 13, 2025

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles
Published on: October 18, 2024
PDZD8 links organelle crosstalk to synaptic remodeling via autophagy
Rajan S Thakur1, Kate M O'Connor-Giles1,2
1Department of Neuroscience, Brown University, Providence, RI, USA.
Abstract:
Synapse formation and plasticity require coordinating cellular processes from signaling to protein turnover over long distances, placing high demands on intracellular communication. Membrane contact sites (MCSs) between organelles are specialized compartments for coordinating cellular processes, yet their functions in the developing nervous system remain poorly understood. Through an in vivo CRISPR screen in Drosophila, we identified the conserved endoplasmic reticulum (ER) MCS tethering protein Pdzd8 as a regulator of activity-dependent synapse development. Our in vivo studies demonstrate that Pdzd8 functions at ER-late endosome/lysosome MCSs to promote lysosomal maturation and increase autophagic flux during periods of high demand such as prolonged neuronal activity.
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