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

Honigmann, A.; van den Bogaart, G.; Iraheta, E.; Risselada, H. J.; Milovanovic, D.; Müller, V.; Müller, S.; Diederichsen, U.; Fasshauer, D.; Grubmüller, H.; Hell, S. W.; Eggeling, C.; Kühnel, K.; Jahn, R.

doi:10.1038/nsmb.2570

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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;

/persons/resource/persons14875

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

/persons/resource/persons32615

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

/persons/resource/persons41506

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

/persons/resource/persons40296

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

/persons/resource/persons15051

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

/persons/resource/persons15155

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

/persons/resource/persons15210

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

/persons/resource/persons15024

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

/persons/resource/persons15388

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

/persons/resource/persons15266

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

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1752416_Supplement_1.pdf
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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.