Single-molecule bouncing at a liquid interface governs presynaptic enrichment

In live Drosophila motor neuron presynapses, alpha-synuclein shows rapid, frequent “bouncing” at a presynaptic liquid-like interface that impedes escape and governs enrichment.

• Why it matters: Presynaptic enrichment is puzzling because enriched cytoplasmic proteins remain highly diffusive, leaving uncertainty about how localization occurs without strong immobilization or diffusion slowing.
• What they did: Using in vivo single-molecule microscopy, the authors tracked diffusion of -Syn and synaptic vesicles in live Drosophila larvae and quantified escape probabilities at the presynaptic interface.
• The result: Impeding escape at the interface, without dramatically slowing diffusion, is sufficient for presynaptic enrichment, and the liquid-like interface aligns with the SV cluster boundary that is required as a scaffold.

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