Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses
Synapsins cluster synaptic vesicles (SVs) to provide a reserve pool (RP) of SVs that maintains synaptic transmission during sustained activity. However, it is unclear how synapsins cluster SVs. Here we show that either liquid-liquid phase separation (LLPS) or tetramerization-dependent cross-linking...
| Main Authors: | , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2023
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/171043 |
| _version_ | 1811683560674820096 |
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| author | Song, Sang-Ho Augustine, George James |
| author2 | Lee Kong Chian School of Medicine (LKCMedicine) |
| author_facet | Lee Kong Chian School of Medicine (LKCMedicine) Song, Sang-Ho Augustine, George James |
| author_sort | Song, Sang-Ho |
| collection | NTU |
| description | Synapsins cluster synaptic vesicles (SVs) to provide a reserve pool (RP) of SVs that maintains synaptic transmission during sustained activity. However, it is unclear how synapsins cluster SVs. Here we show that either liquid-liquid phase separation (LLPS) or tetramerization-dependent cross-linking can cluster SVs, depending on whether a synapse is excitatory or inhibitory. Cell-free reconstitution reveals that both mechanisms can cluster SVs, with tetramerization being more effective. At inhibitory synapses, perturbing synapsin-dependent LLPS impairs SV clustering and synchronization of gamma-aminobutyric acid (GABA) release, while preventing synapsin tetramerization does not. At glutamatergic synapses, the opposite is true: synapsin tetramerization enhances clustering of glutamatergic SVs and mobilization of these SVs from the RP, while synapsin LLPS does not. Comparison of inhibitory and excitatory transmission during prolonged synaptic activity reveals that synapsin LLPS serves as a brake to limit GABA release, while synapsin tetramerization enables rapid mobilization of SVs from the RP to sustain glutamate release. |
| first_indexed | 2024-10-01T04:14:41Z |
| format | Journal Article |
| id | ntu-10356/171043 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:14:41Z |
| publishDate | 2023 |
| record_format | dspace |
| spelling | ntu-10356/1710432023-11-22T00:55:53Z Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses Song, Sang-Ho Augustine, George James Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Neuroscience Liquid-Liquid Phase Separation Synapsins Synaptic Vesicle Trafficking Oligomerization Synapsins cluster synaptic vesicles (SVs) to provide a reserve pool (RP) of SVs that maintains synaptic transmission during sustained activity. However, it is unclear how synapsins cluster SVs. Here we show that either liquid-liquid phase separation (LLPS) or tetramerization-dependent cross-linking can cluster SVs, depending on whether a synapse is excitatory or inhibitory. Cell-free reconstitution reveals that both mechanisms can cluster SVs, with tetramerization being more effective. At inhibitory synapses, perturbing synapsin-dependent LLPS impairs SV clustering and synchronization of gamma-aminobutyric acid (GABA) release, while preventing synapsin tetramerization does not. At glutamatergic synapses, the opposite is true: synapsin tetramerization enhances clustering of glutamatergic SVs and mobilization of these SVs from the RP, while synapsin LLPS does not. Comparison of inhibitory and excitatory transmission during prolonged synaptic activity reveals that synapsin LLPS serves as a brake to limit GABA release, while synapsin tetramerization enables rapid mobilization of SVs from the RP to sustain glutamate release. National Medical Research Council (NMRC) Published version This research was supported by grant OFIRG/MOH-000225-00 from the Singapore National Medical Research Council. 2023-10-10T07:16:18Z 2023-10-10T07:16:18Z 2023 Journal Article Song, S. & Augustine, G. J. (2023). Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses. Cell Reports, 42(8), 113004-. https://dx.doi.org/10.1016/j.celrep.2023.113004 2211-1247 https://hdl.handle.net/10356/171043 10.1016/j.celrep.2023.113004 37597184 2-s2.0-85168119519 8 42 113004 en OFIRG/MOH-000225-00 Cell Reports © 2023 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). application/pdf |
| spellingShingle | Science::Medicine Neuroscience Liquid-Liquid Phase Separation Synapsins Synaptic Vesicle Trafficking Oligomerization Song, Sang-Ho Augustine, George James Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title | Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title_full | Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title_fullStr | Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title_full_unstemmed | Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title_short | Different mechanisms of synapsin-induced vesicle clustering at inhibitory and excitatory synapses |
| title_sort | different mechanisms of synapsin induced vesicle clustering at inhibitory and excitatory synapses |
| topic | Science::Medicine Neuroscience Liquid-Liquid Phase Separation Synapsins Synaptic Vesicle Trafficking Oligomerization |
| url | https://hdl.handle.net/10356/171043 |
| work_keys_str_mv | AT songsangho differentmechanismsofsynapsininducedvesicleclusteringatinhibitoryandexcitatorysynapses AT augustinegeorgejames differentmechanismsofsynapsininducedvesicleclusteringatinhibitoryandexcitatorysynapses |