ER-associated control of axonal vesicle trafficking during neuronal development

In rat hippocampal neurons, axonal vesicle transport shows a transient developmental slowdown linked to increased tripartite ER-vesicle-microtubule interfaces, with PRG1 modulating retention at these sites.

• Why it matters: Axonal vesicle trafficking is required for presynaptic assembly, but the intracellular structures that coordinate vesicle movement during development were unclear.
• What they did: Live confocal and cryo-electron microscopy tracked transport while proximity biotinylation identified ER protein PRG1, which interacts with KIF5A to regulate vesicle retention at ER contact sites.
• The result: A disease-associated PRG1 mutant fails to regulate trafficking, and PRG1 modulation delays synapse formation while preventing network hyperactivity, acting as a developmental checkpoint.

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