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 m...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2013
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| _version_ | 1797103326620286976 |
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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. |
| first_indexed | 2024-03-07T06:18:32Z |
| format | Journal article |
| id | oxford-uuid:f1ea37ac-b54f-4e77-b21d-d82f2de006df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:18:32Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:f1ea37ac-b54f-4e77-b21d-d82f2de006df2022-03-27T11:59:39ZPhosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f1ea37ac-b54f-4e77-b21d-d82f2de006dfEnglishSymplectic 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. |
| 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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