ArticleProceedings of the National Academy of Sciences of the United States of America2026
Alternative splicing of synaptotagmin 7 regulates oligomerization and short-term synaptic plasticity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Alternative splicing of synaptotagmin 7 regulates oligomerization and short-term synaptic plasticity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
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8 authors.
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Abstract
Synaptic plasticity is crucial for learning and memory. The presynaptic calcium sensor synaptotagmin 7 (syt7) regulates aspects of short-term plasticity (STP), but the underlying mechanisms remain unclear. Here, we show that alternative splicing of the syt7 juxtamembrane linker acts as a molecular switch at both biochemical and functional levels. The α and β variants undergo liquid-liquid phase separation to form condensates, while the γ variant forms aggregates. Using iGluSnFR imaging, we found that, when expressed at equal levels, these three isoforms also diverge regarding their abilities to regulate two key aspects of STP: paired-pulse facilitation and synaptic depression. Stimulated emission depletion microscopy showed that all three isoforms form active zone-associated clusters that colocalize with syt1, while minimal photon flux superresolution microscopy resolved syt7 clusters within the active zone, well-positioned to directly control synaptic vesicle dynamics. Thus, alternative splicing might fine-tune STP by differentially impacting syt7 oligomerization.
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