Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation
Abstract
The distance between CaV2.1 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 CaV2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two CaV2.1 splice isoforms (CaV2.1[EFa] and CaV2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that CaV2.1[EFa] is more tightly co-localized with presynaptic markers than CaV2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of CaV2.1 channels.
Funding source: Fondazione Telethon
Award Identifier / Grant number: GGP19181
Acknowledgments
This work was supported by the Telethon foundation (proposal ID: GGP19181 to LAC).
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Research ethics: All animal procedures were in accordance with the guidelines for animal welfare used in scientific research of the Italian Government and the local governance.
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Author contributions: AT and LAC concieved the project. AT, FJ, GB and LAC designed experiments. AT, FJ and JM performed experiments, AT and FJ analysed data, AT, FJ and LAC prepared figures and wrote the paper. The authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors state no conflict of interest.
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Research funding: Telethon foundation, proposal GGP19181.
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Data availability: The raw data can be obtained on request from the corresponding author.
References
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Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/hsz-2023-0235).
© 2023 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Highlights in biochemistry Bochum 2022
- Highlights in biochemistry Bochum 2022
- Two are not enough: synthetic strategies and applications of unnatural base pairs
- The emerging role of ATP as a cosolute for biomolecular processes
- Intracellular spatially-targeted chemical chaperones increase native state stability of mutant SOD1 barrel
- Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation
- Rodent models for mood disorders – understanding molecular changes by investigating social behavior
- Why do certain cancer cells alter functionality and fuse?
- Research Articles/Short Communications
- Cell Biology and Signaling
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Artikel in diesem Heft
- Frontmatter
- Highlights in biochemistry Bochum 2022
- Highlights in biochemistry Bochum 2022
- Two are not enough: synthetic strategies and applications of unnatural base pairs
- The emerging role of ATP as a cosolute for biomolecular processes
- Intracellular spatially-targeted chemical chaperones increase native state stability of mutant SOD1 barrel
- Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation
- Rodent models for mood disorders – understanding molecular changes by investigating social behavior
- Why do certain cancer cells alter functionality and fuse?
- Research Articles/Short Communications
- Cell Biology and Signaling
- MicroRNA-101-3p inhibits nasopharyngeal carcinoma cell proliferation and cisplatin resistance through ZIC5 down-regulation by targeting SOX2