Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release
9 affiliations
- 1Institute for Neuroscience and Cardiovascular Research, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh, Scotland, UK.
- 2Muir Maxwell Epilepsy Centre, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh, Scotland, UK.
- 3Simons Initiative for the Developing Brain, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh, Scotland, UK.
- 4Department of Cell Biology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
- 5Center for Cell Dynamics, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
- 6Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Neurophysiology, Charitéplatz 1, Berlin, Germany.
- 7The Roslin Institute 3D Volume Electron Microscopy Capability, Proteomics and Metabolomics Facility, The Roslin Institute, Royal (Dick) School of Veterinary Studies, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland, UK.
- 8Johannes Gutenberg University Mainz, Institute of Developmental Biology and Neurobiology, AG Functional Neurobiology, Biocenter 1, Hanns-Dieter Hüsch Weg 15, Mainz, Germany.
- 9Kinases and Brain Development Lab, The Francis Crick Institute, London, UK.
Abstract
Synaptic plasticity is the principal mechanism by which neural circuits compute and adapt. Presynaptic plasticity is traditionally regarded as a transient adaptation of the synaptic vesicle fusion and recycling machinery, whereas the role of structural remodeling of synaptic boutons remains unclear. Here, we demonstrate a mechanical coupling between presynaptic structural remodeling and synaptic efficacy. We find that dynamic presynaptic filopodia emerge during active synaptic transmission and deform synaptic boutons while forming transient contacts with postsynaptic structures, which we term neuronal kinapses. Filopodia formation is activity dependent and occurs in intact circuits and human brain. Mechanistically, filopodial growth induces convective in-plane membrane flow toward the filopodium, accelerating release site clearance, a process associated with sustained release probability during repeated synaptic vesicle fusion. As a result, filopodia formation favors an increase in synchronous over asynchronous neurotransmitter release. These results indicate that presynaptic structural remodeling can alter the spatial organization of neurotransmission and, through the membrane flow it generates, modulate its temporal precision.
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BibTeX
@article{jain2026presynaptic,
title = {{Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release}},
author = {Akanksha Jain and Rico Dong and Jana Kroll and Jack F. Webster and Jon Moss and Arthur Bikbaev and Sila K. Ultanir and Alfredo Gonzalez-Sulser and Christian Rosenmund and Martin Heine and Jian Liu and Michael A. Cousin and Daniela Ivanova},
journal = {Science Advances},
year = {2026},
month = oct,
doi = {10.1126/sciadv.aei2661},
url = {https://www.science.org/doi/abs/10.1126/sciadv.aei2661},
note = {CC BY},
}
RIS
TY - JOUR
TI - Presynaptic filopodia form kinapses and promote convective membrane flow to sustain synchronous neurotransmitter release
AU - Akanksha Jain
AU - Rico Dong
AU - Jana Kroll
AU - Jack F. Webster
AU - Jon Moss
AU - Arthur Bikbaev
AU - Sila K. Ultanir
AU - Alfredo Gonzalez-Sulser
AU - Christian Rosenmund
AU - Martin Heine
AU - Jian Liu
AU - Michael A. Cousin
AU - Daniela Ivanova
PY - 2026
DA - 2026/10/28
JO - Science Advances
DO - 10.1126/sciadv.aei2661
UR - https://www.science.org/doi/abs/10.1126/sciadv.aei2661
AB - Synaptic plasticity is the principal mechanism by which neural circuits compute and adapt. Presynaptic plasticity is traditionally regarded as a transient adaptation of the synaptic vesicle fusion and recycling machinery, whereas the role of structural remodeling of synaptic boutons remains unclear. Here, we demonstrate a mechanical coupling between presynaptic structural remodeling and synaptic efficacy. We find that dynamic presynaptic filopodia emerge during active synaptic transmission and deform synaptic boutons while forming transient contacts with postsynaptic structures, which we term neuronal kinapses. Filopodia formation is activity dependent and occurs in intact circuits and human brain. Mechanistically, filopodial growth induces convective in-plane membrane flow toward the filopodium, accelerating release site clearance, a process associated with sustained release probability during repeated synaptic vesicle fusion. As a result, filopodia formation favors an increase in synchronous over asynchronous neurotransmitter release. These results indicate that presynaptic structural remodeling can alter the spatial organization of neurotransmission and, through the membrane flow it generates, modulate its temporal precision.
SN - 2375-2548
ER -