Cross-linking of Phospholipid Membranes is a Conserved Property of Calcium-sensitive Synaptotagmins

Emma Connell, Asiya Giniatullina, Joséphine Lai-Kee-Him, Richard Tavare, Enrico Ferrari, Alan Roseman, Dan Cojoc, Alain R. Brisson, Bazbek Davletov

    Research output: Contribution to journalArticlepeer-review


    Synaptotagmins are vesicular proteins implicated in many membrane trafficking events. They are highly conserved in evolution and the mammalian family contains 16 isoforms. We now show that the tandem C2 domains of several calcium-sensitive synaptotagmin isoforms tested, including Drosophila synaptotagmin, rapidly cross-link phospholipid membranes. In contrast to the tandem structure, individual C2 domains failed to trigger membrane cross-linking in several novel assays. Large-scale liposomal aggregation driven by tandem C2 domains in response to calcium was confirmed by the following techniques: turbidity assay, dynamic light-scattering and both confocal and negative stain electron microscopy. Firm cross-linking of membranes was evident from laser trap experiments. High-resolution cryo-electron microscopy revealed that membrane cross-linking by tandem C2 domains results in a constant distance of ∼9 nm between the apposed membranes. Our findings show the conserved nature of this important property of synaptotagmin, demonstrate the significance of the tandem C2 domain structure and provide a plausible explanation for the accelerating effect of synaptotagmins on membrane fusion. © 2008 Elsevier Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)42-50
    Number of pages8
    JournalJournal of molecular biology
    Issue number1
    Publication statusPublished - 27 Jun 2008


    • C2 domain
    • electron microscopy
    • laser trap
    • membrane cross-linking
    • synaptotagmin


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