Synaptotagmin-1 binds to PIP 2 -containing membrane but not to SNAREs at physiological ionic strength

Yongsoo Park, Jong Bae Seo, Alicia Fraind, Angel Pérez-Lara, Halenur Yavuz, Kyungreem Han, Seung Ryoung Jung, Iman Kattan, Peter Jomo Walla, Mooyoung Choi, David S. Cafiso, Duk Su Koh, Reinhard Jahn*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

91 Citations (Scopus)

Abstract

The Ca 2+ sensor synaptotagmin-1 is thought to trigger membrane fusion by binding to acidic membrane lipids and SNARE proteins. Previous work has shown that binding is mediated by electrostatic interactions that are sensitive to the ionic environment. However, the influence of divalent or polyvalent ions, at physiological concentrations, on synaptotagmin's binding to membranes or SNAREs has not been explored. Here we show that binding of rat synaptotagmin-1 to membranes containing phosphatidylinositol 4,5-bisphosphate (PIP 2) is regulated by charge shielding caused by the presence of divalent cations. Surprisingly, polyvalent ions such as ATP and Mg 2+ completely abrogate synaptotagmin-1 binding to SNAREs regardless of the presence of Ca 2+. Altogether, our data indicate that at physiological ion concentrations Ca 2+ -dependent synaptotagmin-1 binding is confined to PIP 2 -containing membrane patches in the plasma membrane, suggesting that membrane interaction of synaptotagmin-1 rather than SNARE binding triggers exocytosis of vesicles.

Original languageEnglish
Pages (from-to)815-823
Number of pages9
JournalNature Structural and Molecular Biology
Volume22
Issue number10
DOIs
Publication statusPublished - 6 Oct 2015
Externally publishedYes

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