PDZD8 promotes autophagy at ER-lysosome membrane contact sites to regulate activity-dependent synaptic growth.

ABSTRACT: Building synaptic connections requires coordinating a host of cellular activities from cell signaling to protein turnover, placing a high demand on intracellular communication. Membrane contact sites (MCSs) formed between organelles have emerged as key signaling hubs for coordinating diverse cellular activities, yet their roles in the developing nervous system remain obscure. We investigate the in vivo function of the endoplasmic reticulum (ER) MCS tethering and lipid-transfer protein PDZD8, which was recently linked to intellectual disability, in the nervous system. We find that PDZD8 is required for activity-dependent synaptic bouton formation in multiple paradigms. PDZD8 is sufficient to drive excess synaptic bouton formation through an autophagy-dependent mechanism and required for syn

SUBMITTER: Thakur RS 

PROVIDER: S-EPMC12180128 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature