Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission
Summary: The rapid replenishment of release-ready synaptic vesicles (SVs) at a limiting number of presynaptic release sites is required to sustain high-frequency neurotransmission in CNS neurons. Failure to clear release sites from previously exocytosed material has been shown to impair vesicle repl...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719316924 |
| _version_ | 1818291131469791232 |
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| author | Maria Jäpel Fabian Gerth Takeshi Sakaba Jelena Bacetic Lijun Yao Seong-Joo Koo Tanja Maritzen Christian Freund Volker Haucke |
| author_facet | Maria Jäpel Fabian Gerth Takeshi Sakaba Jelena Bacetic Lijun Yao Seong-Joo Koo Tanja Maritzen Christian Freund Volker Haucke |
| author_sort | Maria Jäpel |
| collection | DOAJ |
| description | Summary: The rapid replenishment of release-ready synaptic vesicles (SVs) at a limiting number of presynaptic release sites is required to sustain high-frequency neurotransmission in CNS neurons. Failure to clear release sites from previously exocytosed material has been shown to impair vesicle replenishment and, therefore, fast neurotransmission. The identity of this material and the machinery that removes it from release sites have remained enigmatic. Here we show that the endocytic scaffold protein intersectin 1 clears release sites by direct SH3 domain-mediated association with a non-canonical proline-rich segment of synaptobrevin assembled into the SNARE complex for neuroexocytosis. Acute structure-based or sustained genetic interference with SNARE complex recognition by intersectin 1 causes a rapid stimulation frequency-dependent depression of neurotransmission due to impaired replenishment of release-ready SVs. These findings identify a key molecular mechanism that underlies exo-endocytic coupling during fast neurotransmitter release at central synapses. : Fast neurotransmission (e.g., during hearing) requires the clearance of exocytosed material from presynaptic release sites. The identity of this material and the machinery involved have remained enigmatic. Jäpel et al. show that the endocytic protein intersectin 1 clears release sites by removal of post-fusion SNARE complexes to enable fast neurotransmission. Keywords: neurotransmission, calyx of Held, hippocampus, synaptic vesicle, exocytosis, endocytosis, release site, active zone, intersectin, SNARE |
| first_indexed | 2024-12-13T02:39:11Z |
| format | Article |
| id | doaj.art-6bb6940910be4bb98a685cfb307b97e0 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T02:39:11Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6bb6940910be4bb98a685cfb307b97e02022-12-22T00:02:20ZengElsevierCell Reports2211-12472020-01-01302409420.e6Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast NeurotransmissionMaria Jäpel0Fabian Gerth1Takeshi Sakaba2Jelena Bacetic3Lijun Yao4Seong-Joo Koo5Tanja Maritzen6Christian Freund7Volker Haucke8Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Molecular Pharmacology & Cell Biology, 13125 Berlin, GermanyFreie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, GermanyDoshisha University, Graduate School of Brain Science, Kyoto 610-0394, JapanLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Molecular Pharmacology & Cell Biology, 13125 Berlin, Germany; Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, GermanyMax-Planck-Institute for Biophysical Chemistry, Department of Membrane Biophysics, 37077 Göttingen, GermanyLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Molecular Pharmacology & Cell Biology, 13125 Berlin, GermanyLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Molecular Pharmacology & Cell Biology, 13125 Berlin, GermanyFreie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, GermanyLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Department of Molecular Pharmacology & Cell Biology, 13125 Berlin, Germany; Freie Universität Berlin, Faculty of Biology, Chemistry, Pharmacy, 14195 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany; Corresponding authorSummary: The rapid replenishment of release-ready synaptic vesicles (SVs) at a limiting number of presynaptic release sites is required to sustain high-frequency neurotransmission in CNS neurons. Failure to clear release sites from previously exocytosed material has been shown to impair vesicle replenishment and, therefore, fast neurotransmission. The identity of this material and the machinery that removes it from release sites have remained enigmatic. Here we show that the endocytic scaffold protein intersectin 1 clears release sites by direct SH3 domain-mediated association with a non-canonical proline-rich segment of synaptobrevin assembled into the SNARE complex for neuroexocytosis. Acute structure-based or sustained genetic interference with SNARE complex recognition by intersectin 1 causes a rapid stimulation frequency-dependent depression of neurotransmission due to impaired replenishment of release-ready SVs. These findings identify a key molecular mechanism that underlies exo-endocytic coupling during fast neurotransmitter release at central synapses. : Fast neurotransmission (e.g., during hearing) requires the clearance of exocytosed material from presynaptic release sites. The identity of this material and the machinery involved have remained enigmatic. Jäpel et al. show that the endocytic protein intersectin 1 clears release sites by removal of post-fusion SNARE complexes to enable fast neurotransmission. Keywords: neurotransmission, calyx of Held, hippocampus, synaptic vesicle, exocytosis, endocytosis, release site, active zone, intersectin, SNAREhttp://www.sciencedirect.com/science/article/pii/S2211124719316924 |
| spellingShingle | Maria Jäpel Fabian Gerth Takeshi Sakaba Jelena Bacetic Lijun Yao Seong-Joo Koo Tanja Maritzen Christian Freund Volker Haucke Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission Cell Reports |
| title | Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission |
| title_full | Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission |
| title_fullStr | Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission |
| title_full_unstemmed | Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission |
| title_short | Intersectin-Mediated Clearance of SNARE Complexes Is Required for Fast Neurotransmission |
| title_sort | intersectin mediated clearance of snare complexes is required for fast neurotransmission |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719316924 |
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