1. Structural Biology and Molecular Biophysics
  2. Neuroscience

PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium

  1. Ángel Pérez-Lara
  2. Anusa Thapa
  3. Sarah B Nyenhuis
  4. David A Nyenhuis
  5. Partho Halder
  6. Michael Tietzel
  7. Kai Tittmann
  8. David S Cafiso  Is a corresponding author
  9. Reinhard Jahn  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
  2. University of Virginia, United States
  3. Georg-August University Göttingen, Germany
  4. Georg-August University, Germany
https://doi.org/10.7554/eLife.15886
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Cite this article
  1. Ángel Pérez-Lara
  2. Anusa Thapa
  3. Sarah B Nyenhuis
  4. David A Nyenhuis
  5. Partho Halder
  6. Michael Tietzel
  7. Kai Tittmann
  8. David S Cafiso
  9. Reinhard Jahn
(2016)
PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium
eLife 5:e15886.
https://doi.org/10.7554/eLife.15886
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Abstract

The Ca2+-sensor synaptotagmin-1 that triggers neuronal exocytosis binds to negatively charged membrane lipids (mainly phosphatidylserine, PtdSer, and phosphoinositides, PtdIns) but the molecular details of this process are not fully understood. Using quantitative thermodynamic, kinetic and structural methods we show that synaptotagmin-1 (from Rattus norvegicus and expressed in E.coli) binds to PtdIns(4,5)P2 via a polybasic lysine patch in the C2B domain, which may promote priming/docking of synaptic vesicles. Ca2+ neutralizes the negative charges of the Ca2+ binding sites, resulting in the penetration of synaptotagmin-1 into the membrane, via binding of PtdSer, and the increase of the affinity of the polybasic lysine patch to PtdIns(4,5)P2. These Ca2+-induced events decrease the dissociation rate of synaptotagmin-1 membrane binding while the association rate remains unchanged. We conclude that both membrane penetration and the increased residence time of synaptotagmin-1 at the plasma membrane are crucial for triggering exocytotic membrane fusion.

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Author details

  1. Ángel Pérez-Lara

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2736-3501

  2. Anusa Thapa

    Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.

  3. Sarah B Nyenhuis

    Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.

  4. David A Nyenhuis

    Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States
    Competing interests
    No competing interests declared.

  5. Partho Halder

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    No competing interests declared.

  6. Michael Tietzel

    Department of Molecular Enzymology, Göttingen Center for Molecular Biosciences, Georg-August University Göttingen, Göttingen, Germany
    Competing interests
    No competing interests declared.

  7. Kai Tittmann

    Department of Molecular Enzymology, Göttingen Center for Molecular Biosciences, Georg-August University, Göttingen, Germany
    Competing interests
    No competing interests declared.

  8. David S Cafiso

    Department of Chemistry and Center for Membrane Biology, University of Virginia, Charlottesville, United States
    For correspondence
    cafiso@virginia.edu
    Competing interests
    No competing interests declared.

  9. Reinhard Jahn

    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    rjahn@gwdg.de
    Competing interests
    Reinhard Jahn, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1542-3498

Funding

National Institutes of Health (P01 GM072694)

  • David S Cafiso
  • Reinhard Jahn

Deutsche Forschungsgemeinschaft (SFB803)

  • Ángel Pérez-Lara
  • Partho Halder
  • Reinhard Jahn

Max-Planck-Gesellschaft (Postdoctoral Fellowship)

  • Ángel Pérez-Lara
  • Partho Halder

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2016, Pérez-Lara et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ángel Pérez-Lara
  2. Anusa Thapa
  3. Sarah B Nyenhuis
  4. David A Nyenhuis
  5. Partho Halder
  6. Michael Tietzel
  7. Kai Tittmann
  8. David S Cafiso
  9. Reinhard Jahn
(2016)
PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium
eLife 5:e15886.
https://doi.org/10.7554/eLife.15886

Share this article

https://doi.org/10.7554/eLife.15886

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