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Journal Article

Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment.

MPS-Authors
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Honigmann,  A.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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van den Bogaart,  G.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Risselada,  H. J.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

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Milovanovic,  D.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Müller,  V.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Fasshauer,  D.
Research Group of Structural Biochemistry, MPI for biophysical chemistry, Max Planck Society;

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Grubmüller,  H.
Department of Theoretical and Computational Biophysics, MPI for biophysical chemistry, Max Planck Society;

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Hell,  S. W.       
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Eggeling,  C.
Department of NanoBiophotonics, MPI for biophysical chemistry, Max Planck Society;

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Kühnel,  K.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Jahn,  R.
Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society;

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Fulltext (public)

1752416.pdf
(Publisher version), 3MB

Supplementary Material (public)

1752416_Supplement_1.pdf
(Supplementary material), 2MB

Citation

Honigmann, A., van den Bogaart, G., Iraheta, E., Risselada, H. J., Milovanovic, D., Müller, V., et al. (2013). Phosphatidylinositol 4,5-bisphosphate clusters act as molecular beacons for vesicle recruitment. Nature Structural and Molecular Biology, 20, 679-686. doi:10.1038/nsmb.2570.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0013-7673-7
Abstract
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.