Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment
Synaptic-vesicle exocytosis is mediated by the vesicular Ca 2+ sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering me...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797088353475100672 |
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| author | Honigmann, A Van Den Bogaart, G Iraheta, E Risselada, H Milovanovic, D Mueller, V Müllar, S Diederichsen, U Fasshauer, D Grubmüller, H Hell, S Eggeling, C Kühnel, K Jahn, R |
| author_facet | Honigmann, A Van Den Bogaart, G Iraheta, E Risselada, H Milovanovic, D Mueller, V Müllar, S Diederichsen, U Fasshauer, D Grubmüller, H Hell, S Eggeling, C Kühnel, K Jahn, R |
| author_sort | Honigmann, A |
| collection | OXFORD |
| description | Synaptic-vesicle exocytosis is mediated by the vesicular Ca 2+ sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering membrane fusion. Using PC12 cells from Rattus norvegicus and artificial supported bilayers, we show that synaptotagmin-1 interacts with the polybasic linker region of syntaxin-1A independent of Ca 2+ through PIP2. This interaction allows both Ca 2+ -binding sites of synaptotagmin-1 to bind to phosphatidylserine in the vesicle membrane upon Ca 2+ triggering. We determined the crystal structure of the C2B domain of synaptotagmin-1 bound to phosphoserine, allowing development of a high-resolution model of synaptotagmin bridging two different membranes. Our results suggest that PIP2 clusters organized by syntaxin-1 act as molecular beacons for vesicle docking, with the subsequent Ca 2+ influx bringing the vesicle membrane close enough for membrane fusion. © 2013 Nature America, Inc. All rights reserved. |
| first_indexed | 2024-03-07T02:48:49Z |
| format | Journal article |
| id | oxford-uuid:acfa1598-64ea-4adc-be2e-da9f42417a17 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:48:49Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:acfa1598-64ea-4adc-be2e-da9f42417a172022-03-27T03:32:29ZPhosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitmentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:acfa1598-64ea-4adc-be2e-da9f42417a17EnglishSymplectic Elements at Oxford2013Honigmann, AVan Den Bogaart, GIraheta, ERisselada, HMilovanovic, DMueller, VMüllar, SDiederichsen, UFasshauer, DGrubmüller, HHell, SEggeling, CKühnel, KJahn, RSynaptic-vesicle exocytosis is mediated by the vesicular Ca 2+ sensor synaptotagmin-1. Synaptotagmin-1 interacts with the SNARE protein syntaxin-1A and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2). However, it is unclear how these interactions contribute to triggering membrane fusion. Using PC12 cells from Rattus norvegicus and artificial supported bilayers, we show that synaptotagmin-1 interacts with the polybasic linker region of syntaxin-1A independent of Ca 2+ through PIP2. This interaction allows both Ca 2+ -binding sites of synaptotagmin-1 to bind to phosphatidylserine in the vesicle membrane upon Ca 2+ triggering. We determined the crystal structure of the C2B domain of synaptotagmin-1 bound to phosphoserine, allowing development of a high-resolution model of synaptotagmin bridging two different membranes. Our results suggest that PIP2 clusters organized by syntaxin-1 act as molecular beacons for vesicle docking, with the subsequent Ca 2+ influx bringing the vesicle membrane close enough for membrane fusion. © 2013 Nature America, Inc. All rights reserved. |
| spellingShingle | Honigmann, A Van Den Bogaart, G Iraheta, E Risselada, H Milovanovic, D Mueller, V Müllar, S Diederichsen, U Fasshauer, D Grubmüller, H Hell, S Eggeling, C Kühnel, K Jahn, R Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title | Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title_full | Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title_fullStr | Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title_full_unstemmed | Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title_short | Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment |
| title_sort | phosphatidylinositol 4 5 bisphosphate clusters act as molecular beacons for vesicle recruitment |
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