Alternative splicing of synaptotagmin 7 regulates oligomerization and short-term synaptic plasticity.

Authors

Nikunj Mehta, Devin T Larson, Mitch Wozney, Shweta Mishra, Smrithika Subramani, Simi Kaur, Avani Jain, Edwin R Chapman

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 38. Pages e2601714123. Sep 22, 2026. Epub Sep 15, 2026.

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.

PMID:
42743279
Bibliographic data and abstract were imported from PubMed on 16 Sep 2026.

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