Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles
Abstract Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communic...
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Nature Portfolio
2024-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-46256-1 |
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| author | Shanley F. Longfield Rachel S. Gormal Matis Feller Pierre Parutto Jürgen Reingruber Tristan P. Wallis Merja Joensuu George J. Augustine Ramón Martínez-Mármol David Holcman Frédéric A. Meunier |
| author_facet | Shanley F. Longfield Rachel S. Gormal Matis Feller Pierre Parutto Jürgen Reingruber Tristan P. Wallis Merja Joensuu George J. Augustine Ramón Martínez-Mármol David Holcman Frédéric A. Meunier |
| author_sort | Shanley F. Longfield |
| collection | DOAJ |
| description | Abstract Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism. Here, we used Dual-pulse sub-diffractional Tracking of Internalised Molecules (DsdTIM) to simultaneously track single SVs from the recycling and the reserve pools, in live hippocampal neurons. The reserve pool displays a lower presynaptic mobility compared to the recycling pool and is also present in the axons. Triple knockout of Synapsin 1-3 genes (SynTKO) increased the mobility of reserve pool SVs. Re-expression of wild-type Syn2a (Syn2aWT), but not the tetramerization-deficient mutant K337Q (Syn2aK337Q), fully rescued these effects. Single-particle tracking revealed that Syn2aK337QmEos3.1 exhibited altered activity-dependent presynaptic translocation and nanoclustering. Therefore, Syn2a tetramerization controls its own presynaptic nanoclustering and thereby contributes to the dynamic immobilisation of the SV reserve pool. |
| format | Article |
| id | doaj-art-340ae843e8934ea2a097d76a195d9de7 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-340ae843e8934ea2a097d76a195d9de72025-08-20T03:43:11ZengNature PortfolioNature Communications2041-17232024-03-0115111810.1038/s41467-024-46256-1Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesiclesShanley F. Longfield0Rachel S. Gormal1Matis Feller2Pierre Parutto3Jürgen Reingruber4Tristan P. Wallis5Merja Joensuu6George J. Augustine7Ramón Martínez-Mármol8David Holcman9Frédéric A. Meunier10Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandGroup of Data Modelling and Computational Biology, IBENS, Ecole Normale SuperieureGroup of Data Modelling and Computational Biology, IBENS, Ecole Normale SuperieureGroup of Data Modelling and Computational Biology, IBENS, Ecole Normale SuperieureClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandTemasek Lifesciences LaboratoryClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandGroup of Data Modelling and Computational Biology, IBENS, Ecole Normale SuperieureClem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of QueenslandAbstract Neurotransmitter release relies on the regulated fusion of synaptic vesicles (SVs) that are tightly packed within the presynaptic bouton of neurons. The mechanism by which SVs are clustered at the presynapse, while preserving their ability to dynamically recycle to support neuronal communication, remains unknown. Synapsin 2a (Syn2a) tetramerization has been suggested as a potential clustering mechanism. Here, we used Dual-pulse sub-diffractional Tracking of Internalised Molecules (DsdTIM) to simultaneously track single SVs from the recycling and the reserve pools, in live hippocampal neurons. The reserve pool displays a lower presynaptic mobility compared to the recycling pool and is also present in the axons. Triple knockout of Synapsin 1-3 genes (SynTKO) increased the mobility of reserve pool SVs. Re-expression of wild-type Syn2a (Syn2aWT), but not the tetramerization-deficient mutant K337Q (Syn2aK337Q), fully rescued these effects. Single-particle tracking revealed that Syn2aK337QmEos3.1 exhibited altered activity-dependent presynaptic translocation and nanoclustering. Therefore, Syn2a tetramerization controls its own presynaptic nanoclustering and thereby contributes to the dynamic immobilisation of the SV reserve pool.https://doi.org/10.1038/s41467-024-46256-1 |
| spellingShingle | Shanley F. Longfield Rachel S. Gormal Matis Feller Pierre Parutto Jürgen Reingruber Tristan P. Wallis Merja Joensuu George J. Augustine Ramón Martínez-Mármol David Holcman Frédéric A. Meunier Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles Nature Communications |
| title | Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| title_full | Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| title_fullStr | Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| title_full_unstemmed | Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| title_short | Synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| title_sort | synapsin 2a tetramerisation selectively controls the presynaptic nanoscale organisation of reserve synaptic vesicles |
| url | https://doi.org/10.1038/s41467-024-46256-1 |
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