Single-molecule bouncing at a liquid interface governs presynaptic enrichment
- 1Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia
Abstract
Many cellular processes rely on accumulating highly diffusive cytoplasmic proteins to a specific location within the cell. This spatial enrichment is generally thought to rely on locally immobilizing proteins or slowing diffusion through binding and molecular crowding. Paradoxically, cytoplasmic proteins that are enriched within nerve terminals remain highly diffusive, raising questions about the mechanisms that govern presynaptic enrichment. Here, using in vivo single-molecule microscopy, we tracked the diffusion of a model cytoplasmic protein, -Synuclein (-Syn), and synaptic vesicles (SVs), in motor neuron presynapses of live Drosophila larvae. We demonstrate that -Syn undergoes rapid and frequent "bouncing" events at a presynaptic interface, locally impeding escape from the presynapse. We measured escape probabilities at the interface, and show that impeding escape, without dramatically slowing diffusion, is sufficient to govern presynaptic enrichment. The interface is liquid-like and coincides with the boundary of the SV cluster, which is a necessary scaffold for the presynaptic enrichment of -Syn. Our results provide direct evidence of interfacial reflectivity at the interface of liquid-like compartments, and that this phenomenon can govern the subcellular enrichment of proteins and small organelles at the level of individual particles.
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BibTeX
@misc{kudo2026singlemolecule,
title = {{Single-molecule bouncing at a liquid interface governs presynaptic enrichment}},
author = {K. Kudo and S. F. Longfield and A. J. McCann and N. Schoovaerts and J. Sanchez-Velasquez and L. A. Parra-Rivas and S. Roy and P. Verstreken and E. Hinde and S. S. Millard and A. T. Bademosi and F. A. Meunier},
howpublished = {bioRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.01.763503},
url = {https://www.biorxiv.org/content/10.64898/2026.11.01.763503v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Single-molecule bouncing at a liquid interface governs presynaptic enrichment
AU - K. Kudo
AU - S. F. Longfield
AU - A. J. McCann
AU - N. Schoovaerts
AU - J. Sanchez-Velasquez
AU - L. A. Parra-Rivas
AU - S. Roy
AU - P. Verstreken
AU - E. Hinde
AU - S. S. Millard
AU - A. T. Bademosi
AU - F. A. Meunier
PY - 2026
DA - 2026/11/01
PB - bioRxiv
DO - 10.64898/2026.11.01.763503
UR - https://www.biorxiv.org/content/10.64898/2026.11.01.763503v1
AB - Many cellular processes rely on accumulating highly diffusive cytoplasmic proteins to a specific location within the cell. This spatial enrichment is generally thought to rely on locally immobilizing proteins or slowing diffusion through binding and molecular crowding. Paradoxically, cytoplasmic proteins that are enriched within nerve terminals remain highly diffusive, raising questions about the mechanisms that govern presynaptic enrichment. Here, using in vivo single-molecule microscopy, we tracked the diffusion of a model cytoplasmic protein, -Synuclein (-Syn), and synaptic vesicles (SVs), in motor neuron presynapses of live Drosophila larvae. We demonstrate that -Syn undergoes rapid and frequent "bouncing" events at a presynaptic interface, locally impeding escape from the presynapse. We measured escape probabilities at the interface, and show that impeding escape, without dramatically slowing diffusion, is sufficient to govern presynaptic enrichment. The interface is liquid-like and coincides with the boundary of the SV cluster, which is a necessary scaffold for the presynaptic enrichment of -Syn. Our results provide direct evidence of interfacial reflectivity at the interface of liquid-like compartments, and that this phenomenon can govern the subcellular enrichment of proteins and small organelles at the level of individual particles.
ER -