Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro
Abstract Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To inv...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-04779-1 |
| _version_ | 1797831945868017664 |
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| author | Cecilia D. Velasco Rachel Santarella-Mellwig Martin Schorb Li Gao Oliver Thorn-Seshold Artur Llobet |
| author_facet | Cecilia D. Velasco Rachel Santarella-Mellwig Martin Schorb Li Gao Oliver Thorn-Seshold Artur Llobet |
| author_sort | Cecilia D. Velasco |
| collection | DOAJ |
| description | Abstract Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate how the balance between microtubule growth and shrinkage affects neurotransmission we induced synchronous microtubule depolymerization by photoactivation of the chemical inhibitor SBTub3. The consequence was an increase in spontaneous neurotransmitter release. An analogous effect was obtained by dialyzing the cytosol with Kif18A, a plus-end-directed kinesin with microtubule depolymerizing activity. Kif18A also inhibited the refilling of the readily releasable pool of synaptic vesicles during high frequency stimulation. The action of Kif18A was associated to one order of magnitude increases in the numbers of exo-endocytic pits and endosomes present in the presynaptic terminal. An enhancement of spontaneous neurotransmitter release was also observed when neurons were dialyzed with stathmin-1, a protein with a widespread presence in the nervous system that induces microtubule depolymerization. Taken together, these results support that microtubules restrict spontaneous neurotransmitter release as well as promote the replenishment of the readily releasable pool of synaptic vesicles. |
| first_indexed | 2024-04-09T13:59:49Z |
| format | Article |
| id | doaj.art-4335e5bec8904639944a3685fd2cd1b6 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-04-09T13:59:49Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-4335e5bec8904639944a3685fd2cd1b62023-05-07T11:20:49ZengNature PortfolioCommunications Biology2399-36422023-05-016111510.1038/s42003-023-04779-1Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitroCecilia D. Velasco0Rachel Santarella-Mellwig1Martin Schorb2Li Gao3Oliver Thorn-Seshold4Artur Llobet5Laboratory of Neurobiology, Department of Pathology and Experimental Therapy, Institute of Neurosciences, University of BarcelonaElectron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL)Electron Microscopy Core Facility, European Molecular Biology Laboratory (EMBL)Department of Pharmacy, Ludwig-Maximilians University of MunichDepartment of Pharmacy, Ludwig-Maximilians University of MunichLaboratory of Neurobiology, Department of Pathology and Experimental Therapy, Institute of Neurosciences, University of BarcelonaAbstract Microtubules are key to multiple neuronal functions involving the transport of organelles, however, their relationship to neurotransmitter release is still unresolved. Here, we show that microtubules present in the presynaptic compartment of cholinergic autaptic synapses are dynamic. To investigate how the balance between microtubule growth and shrinkage affects neurotransmission we induced synchronous microtubule depolymerization by photoactivation of the chemical inhibitor SBTub3. The consequence was an increase in spontaneous neurotransmitter release. An analogous effect was obtained by dialyzing the cytosol with Kif18A, a plus-end-directed kinesin with microtubule depolymerizing activity. Kif18A also inhibited the refilling of the readily releasable pool of synaptic vesicles during high frequency stimulation. The action of Kif18A was associated to one order of magnitude increases in the numbers of exo-endocytic pits and endosomes present in the presynaptic terminal. An enhancement of spontaneous neurotransmitter release was also observed when neurons were dialyzed with stathmin-1, a protein with a widespread presence in the nervous system that induces microtubule depolymerization. Taken together, these results support that microtubules restrict spontaneous neurotransmitter release as well as promote the replenishment of the readily releasable pool of synaptic vesicles.https://doi.org/10.1038/s42003-023-04779-1 |
| spellingShingle | Cecilia D. Velasco Rachel Santarella-Mellwig Martin Schorb Li Gao Oliver Thorn-Seshold Artur Llobet Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro Communications Biology |
| title | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| title_full | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| title_fullStr | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| title_full_unstemmed | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| title_short | Microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| title_sort | microtubule depolymerization contributes to spontaneous neurotransmitter release in vitro |
| url | https://doi.org/10.1038/s42003-023-04779-1 |
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