1. Structural Biology and Molecular Biophysics
  2. Neuroscience
Download icon

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
Research Article
  • Cited 35
  • Views 1,858
  • Annotations
Cite this article as: eLife 2016;5:e15886 doi: 10.7554/eLife.15886

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.

Article and author information

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.

Reviewing Editor

  1. Axel T Brunger, Stanford University Medical Center, United States

Publication history

  1. Received: March 10, 2016
  2. Accepted: October 25, 2016
  3. Accepted Manuscript published: October 28, 2016 (version 1)
  4. Version of Record published: November 25, 2016 (version 2)

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.

Metrics

  • 1,858
    Page views
  • 651
    Downloads
  • 35
    Citations

Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Structural Biology and Molecular Biophysics
    Keenan C Taylor et al.
    Research Article
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Esteban Suárez-Delgado, León D Islas
    Insight