Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading

Synaptic transmission is mediated by the exocytotic release of neurotransmitters stored in synaptic vesicles (SVs). SVs filled with neurotransmitters preferentially undergo exocytosis, but it is unclear how this is achieved. Here, we show that during transmitter loading, SVs substantially increase in size, which is reversible and requires synaptophysin, an abundant membrane protein with an unclear function. SVs are larger when synaptophysin is knocked out, and conversely, liposomes are smaller when reconstituted with synaptophysin. Moreover, transmitter loading of SVs accelerates fusion in vitro, which is abolished when synaptophysin is lacking despite near normal transmitter uptake. We conclude that synaptophysin functions as a curvature-promoting entity in the SV membrane, allowing for major lateral expansion of the SV membrane during neurotransmitter filling, thus increasing their propensity for exocytosis.

Authors

Institutions

Publication Details

Journal
Science Advances
Published
2025-04-23
DOI
https://doi.org/10.1126/sciadv.ads4661
Citations
5
Primary Topic
Cellular transport and secretion
Type
article
Field-Weighted Citation Impact
5.76
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading

Marcelo Ganzella, Gudrun Ahnert‐Hilger, Sascha Seibert, Julia Preobraschenski et al.
5 citations
Science Advances
Cellular transport and secretion
5.76
article

Synaptophysin accelerates synaptic vesicle fusion by expanding the membrane upon neurotransmitter loading

Marcelo Ganzella, Gudrun Ahnert‐Hilger, Sascha Seibert, Julia Preobraschenski, Lukas K. Tamm, Agnieszka Münster‐Wandowski, Alex J.B. Kreutzberger, Dietmar Riedel, Volker Kiessling, Agata Witkowska, Reinhard Jahn, Mark A. B. Kreutzberger, Linda H. M. Oolsthorn
article en
5 citations

Abstract

Synaptic transmission is mediated by the exocytotic release of neurotransmitters stored in synaptic vesicles (SVs). SVs filled with neurotransmitters preferentially undergo exocytosis, but it is unclear how this is achieved. Here, we show that during transmitter loading, SVs substantially increase in size, which is reversible and requires synaptophysin, an abundant membrane protein with an unclear function. SVs are larger when synaptophysin is knocked out, and conversely, liposomes are smaller when reconstituted with synaptophysin. Moreover, transmitter loading of SVs accelerates fusion in vitro, which is abolished when synaptophysin is lacking despite near normal transmitter uptake. We conclude that synaptophysin functions as a curvature-promoting entity in the SV membrane, allowing for major lateral expansion of the SV membrane during neurotransmitter filling, thus increasing their propensity for exocytosis.

Science AdvancesVol. 11(17)
European Neuroscience Institute Göttingen (DE), Max Planck Institute of Experimental Medicine (DE), University of Virginia (US), University of Göttingen (DE), Charité - Universitätsmedizin Berlin (DE)
Openalex Percentile: Top 4%
Cellular transport and secretion
5.76
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.