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Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion

Author

Listed:
  • Kuang Hu

    (MRC Laboratory of Molecular Biology)

  • Joe Carroll

    (MRC Laboratory of Molecular Biology)

  • Sergei Fedorovich

    (MRC Laboratory of Molecular Biology)

  • Colin Rickman

    (MRC Laboratory of Molecular Biology)

  • Andrei Sukhodub

    (MRC Laboratory of Molecular Biology)

  • Bazbek Davletov

    (MRC Laboratory of Molecular Biology)

Abstract

Release of neurotransmitter occurs when synaptic vesicles fuse with the plasma membrane. This neuronal exocytosis is triggered by calcium and requires three SNARE (soluble-N-ethylmaleimide-sensitive factor attachment protein receptors) proteins: synaptobrevin (also known as VAMP) on the synaptic vesicle, and syntaxin and SNAP-25 on the plasma membrane1,2,3,4. Neuronal SNARE proteins form a parallel four-helix bundle that is thought to drive the fusion of opposing membranes5,6. As formation of this SNARE complex in solution does not require calcium, it is not clear what function calcium has in triggering SNARE-mediated membrane fusion. We now demonstrate that whereas syntaxin and SNAP-25 in target membranes are freely available for SNARE complex formation, availability of synaptobrevin on synaptic vesicles is very limited. Calcium at micromolar concentrations triggers SNARE complex formation and fusion between synaptic vesicles and reconstituted target membranes. Although calcium does promote interaction of SNARE proteins between opposing membranes, it does not act by releasing synaptobrevin from synaptic vesicle restriction. Rather, our data suggest a mechanism in which calcium-triggered membrane apposition enables syntaxin and SNAP-25 to engage synaptobrevin, leading to membrane fusion.

Suggested Citation

  • Kuang Hu & Joe Carroll & Sergei Fedorovich & Colin Rickman & Andrei Sukhodub & Bazbek Davletov, 2002. "Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion," Nature, Nature, vol. 415(6872), pages 646-650, February.
    • Handle: RePEc:nat:nature:v:415:y:2002:i:6872:d:10.1038_415646a
    DOI: 10.1038/415646a
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