Endosomal sorting protein SNX4 limits synaptic vesicle docking and release
Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how SNX4 affects synapse function remains unknown. We generated a conditional SNX4 knock-out mouse model and report that SNX4 cKO synapses show enhanced neurotransmissio...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-12-01
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| Online Access: | https://elifesciences.org/articles/97910 |
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| author | Josse Poppinga Nolan J Barrett L Niels Cornelisse Matthijs Verhage Jan RT van Weering |
| author_facet | Josse Poppinga Nolan J Barrett L Niels Cornelisse Matthijs Verhage Jan RT van Weering |
| author_sort | Josse Poppinga |
| collection | DOAJ |
| description | Sorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how SNX4 affects synapse function remains unknown. We generated a conditional SNX4 knock-out mouse model and report that SNX4 cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. SNX4 depletion did not affect vesicle recycling, basic autophagic flux, or the levels and localization of SNARE-protein VAMP2/synaptobrevin-2. However, SNX4 depletion affected synapse ultrastructure: an increase in docked synaptic vesicles at the active zone, while the overall vesicle number was normal, and a decreased active zone length. These effects together lead to a substantially increased density of docked vesicles per release site. In conclusion, SNX4 is a negative regulator of synaptic vesicle docking and release. These findings suggest a role for SNX4 in synaptic vesicle recruitment at the active zone. |
| format | Article |
| id | doaj-art-19bb95e5cd7e487386f565b01cfab78f |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-19bb95e5cd7e487386f565b01cfab78f2025-08-20T01:58:34ZengeLife Sciences Publications LtdeLife2050-084X2024-12-011310.7554/eLife.97910Endosomal sorting protein SNX4 limits synaptic vesicle docking and releaseJosse Poppinga0https://orcid.org/0009-0002-6809-3832Nolan J Barrett1L Niels Cornelisse2Matthijs Verhage3Jan RT van Weering4https://orcid.org/0000-0001-5259-4945Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, NetherlandsDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, NetherlandsDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, Netherlands; Department of Human Genetics, CNCR, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, Netherlands; Department of Human Genetics, CNCR, Amsterdam UMC, Amsterdam, NetherlandsDepartment of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), VU University, Amsterdam, Netherlands; Department of Human Genetics, CNCR, Amsterdam UMC, Amsterdam, NetherlandsSorting nexin 4 (SNX4) is an evolutionary conserved organizer of membrane recycling. In neurons, SNX4 accumulates in synapses, but how SNX4 affects synapse function remains unknown. We generated a conditional SNX4 knock-out mouse model and report that SNX4 cKO synapses show enhanced neurotransmission during train stimulation, while the first evoked EPSC was normal. SNX4 depletion did not affect vesicle recycling, basic autophagic flux, or the levels and localization of SNARE-protein VAMP2/synaptobrevin-2. However, SNX4 depletion affected synapse ultrastructure: an increase in docked synaptic vesicles at the active zone, while the overall vesicle number was normal, and a decreased active zone length. These effects together lead to a substantially increased density of docked vesicles per release site. In conclusion, SNX4 is a negative regulator of synaptic vesicle docking and release. These findings suggest a role for SNX4 in synaptic vesicle recruitment at the active zone.https://elifesciences.org/articles/97910neurotranmissionvesicle recruitmentplasticityrecycling endosomehippocampal neuron |
| spellingShingle | Josse Poppinga Nolan J Barrett L Niels Cornelisse Matthijs Verhage Jan RT van Weering Endosomal sorting protein SNX4 limits synaptic vesicle docking and release eLife neurotranmission vesicle recruitment plasticity recycling endosome hippocampal neuron |
| title | Endosomal sorting protein SNX4 limits synaptic vesicle docking and release |
| title_full | Endosomal sorting protein SNX4 limits synaptic vesicle docking and release |
| title_fullStr | Endosomal sorting protein SNX4 limits synaptic vesicle docking and release |
| title_full_unstemmed | Endosomal sorting protein SNX4 limits synaptic vesicle docking and release |
| title_short | Endosomal sorting protein SNX4 limits synaptic vesicle docking and release |
| title_sort | endosomal sorting protein snx4 limits synaptic vesicle docking and release |
| topic | neurotranmission vesicle recruitment plasticity recycling endosome hippocampal neuron |
| url | https://elifesciences.org/articles/97910 |
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