{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Mehta N"],"funding":["NIMH NIH HHS","NHGRI NIH HHS","NINDS NIH HHS"],"pubmed_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. Further, MINFLUX super resolution microscopy demonstrated that syt7 forms clusters in the active zone, well-positioned to directly control synaptic vesicle dynamics. Thus, alternative splicing might fine-tune STP by differentially impacting syt7 oligomerization."],"journal":["bioRxiv : the preprint server for biology"],"pagination":["2025.10.27.684894"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12636619"],"repository":["biostudies-literature"],"pubmed_title":["Alternative splicing of synaptotagmin 7 regulates oligomerization and short-term synaptic plasticity."],"pmcid":["PMC12636619"],"funding_grant_id":["UM1 HG006348","R35 NS136306","R01 MH061876"],"pubmed_authors":["Mehta N","Jain A","Salaka RJ","Subramani S","Mishra S","Wozney M","Chapman ER","Larson DT","Kaur S"],"additional_accession":[]},"is_claimable":false,"name":"Alternative splicing of synaptotagmin 7 regulates oligomerization and short-term synaptic plasticity.","description":"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. Further, MINFLUX super resolution microscopy demonstrated that syt7 forms clusters in the active zone, well-positioned to directly control synaptic vesicle dynamics. Thus, alternative splicing might fine-tune STP by differentially impacting syt7 oligomerization.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-02T03:11:08.447Z","creation":"2026-06-02T03:09:05.245Z"},"accession":"S-EPMC12636619","cross_references":{"pubmed":["41278746"],"doi":["10.1101/2025.10.27.684894"]}}