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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Alf Honigmann - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Geert Van Den Bogaart - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), Radboud University Nijmegen (Author)
  • Emilio Iraheta - , University of Lausanne (Author)
  • H. Jelger Risselada - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Dragomir Milovanovic - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Veronika Mueller - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Stefan Müllar - , University of Göttingen (Author)
  • Ulf Diederichsen - , University of Göttingen (Author)
  • Dirk Fasshauer - , University of Lausanne (Author)
  • Helmut Grubmüller - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Stefan W. Hell - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Christian Eggeling - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute), University of Oxford (Author)
  • Karin Kühnel - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)
  • Reinhard Jahn - , Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute) (Author)

Abstract

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.

Details

Original languageEnglish
Pages (from-to)679-686
Number of pages8
JournalNature Structural and Molecular Biology
Volume20
Issue number6
Publication statusPublished - Jun 2013
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 23665582
ORCID /0000-0003-0475-3790/work/161889561

Keywords

ASJC Scopus subject areas