The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment
Open accessAbstract
Synaptic-vesicle exocytosis is mediated by the vesicular Ca2+ 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 Ca2+ through PIP2. This interaction allows both Ca2+-binding sites of synaptotagmin-1 to bind to phosphatidylserine in the vesicle membrane upon Ca2+ 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 Ca2+ influx bringing the vesicle membrane close enough for membrane fusion.
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Metadata
- Authors
- Honigmann, A., van den Bogaart, G., Iraheta, E., Risselada, H. J., Milovanovic, D., Mueller, V., Müllar, S., Diederichsen, U., Fasshauer, D., Grubmüller, H., Hell, S. W., Eggeling, C., Kühnel, K., & Jahn, R.
- Venue
- Nature Structural & Molecular Biology
- Published
- 2013-05-12
- Volume
- 20
- Issue
- 6
- Pages
- 679-686
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W1978302530
- Cited by
- 279
- References
- 55
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Honigmann, A., van den Bogaart, G., Iraheta, E., Risselada, H. J., Milovanovic, D., Mueller, V., Müllar, S., Diederichsen, U., Fasshauer, D., Grubmüller, H., Hell, S. W., Eggeling, C., Kühnel, K., & Jahn, R. (2013). Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment. Nature Structural & Molecular Biology. https://doi.org/10.1038/nsmb.2570
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