Mechanism and function of synaptotagmin-mediated membrane apposition.

Journal Article (Journal Article)

Synaptotagmin-1 is a Ca(2+) sensor that triggers synchronous neurotransmitter release. The first documented biochemical property of synaptotagmin-1 was its ability to aggregate membranes in response to Ca(2+). However, the mechanism and function of this process were poorly understood. Here we show that synaptotagmin-1-mediated vesicle aggregation is driven by trans interactions between synaptotagmin-1 molecules bound to different membranes. We found a strong correlation between the ability of Ca(2+)-bound synaptotagmin-1 to aggregate vesicles and to stimulate SNARE-mediated membrane fusion. Moreover, artificial aggregation of membranes-using non-synaptotagmin proteins-also efficiently promoted fusion of SNARE-bearing liposomes. Finally, using a modified fusion assay, we observed that synaptotagmin-1 drove the assembly of otherwise non-fusogenic individual t-SNARE proteins into fusion-competent heterodimers, independently of aggregation. Thus, membrane aggregation and t-SNARE assembly appear to be two key aspects of fusion reactions that are regulated by Ca(2+)-bound synaptotagmin-1 and catalyzed by SNAREs.

Full Text

Duke Authors

Cited Authors

  • Hui, E; Gaffaney, JD; Wang, Z; Johnson, CP; Evans, CS; Chapman, ER

Published Date

  • June 5, 2011

Published In

Volume / Issue

  • 18 / 7

Start / End Page

  • 813 - 821

PubMed ID

  • 21642967

Pubmed Central ID

  • PMC3130839

Electronic International Standard Serial Number (EISSN)

  • 1545-9985

Digital Object Identifier (DOI)

  • 10.1038/nsmb.2075


  • eng

Conference Location

  • United States