biostudies-literatureCingolani LATelethon931-937https://www.ebi.ac.uk/biostudies/studies/S-EPMC10695435biostudies-literatureUnknown404(10)The distance between Ca_V2.1 voltage-gated Ca²⁺ channels and the Ca²⁺ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca_V2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two Ca_V2.1 splice isoforms (Ca_V2.1[EFa] and Ca_V2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that Ca_V2.1[EFa] is more tightly co-localized with presynaptic markers than Ca_V2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of Ca_V2.1 channels.Biological chemistryNanoscale organization of Ca_V2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.PMC10695435GGP19181Jaudon FThalhammer AMuia JBaj GCingolani LAfalseNanoscale organization of Ca_V2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.The distance between Ca_V2.1 voltage-gated Ca²⁺ channels and the Ca²⁺ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of Ca_V2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two Ca_V2.1 splice isoforms (Ca_V2.1[EFa] and Ca_V2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that Ca_V2.1[EFa] is more tightly co-localized with presynaptic markers than Ca_V2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of Ca_V2.1 channels.2023-01-01T00:00:00Z2023 Sep2026-05-29T00:41:07.396Z2025-04-06T05:35:41.566ZS-EPMC106954353765857810.1515/hsz-2023-0235