PtdInsP2 and PtdSer cooperate to trap synaptotagmin-1 to the plasma membrane in the presence of calcium
- Max Planck Institute for Biophysical Chemistry, Germany
- University of Virginia, United States
- Georg-August University Göttingen, Germany
- Georg-August University, Germany
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
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
- Axel T Brunger, Stanford University Medical Center, United States
Version history
- Received: March 10, 2016
- Accepted: October 25, 2016
- Accepted Manuscript published: October 28, 2016 (version 1)
- 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.
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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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