Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18463-8. doi: 10.1073/pnas.1006727107. Epub 2010 Oct 11.

Role of the synaptobrevin C terminus in fusion pore formation.

Author information

1
School of Applied and Engineering Physics, 212 Clark Hall, Cornell University, Ithaca, NY 14853, USA.

Abstract

Neurotransmitter release is mediated by the SNARE proteins synaptobrevin II (sybII, also known as VAMP2), syntaxin, and SNAP-25, generating a force transfer to the membranes and inducing fusion pore formation. However, the molecular mechanism by which this force leads to opening of a fusion pore remains elusive. Here we show that the ability of sybII to support exocytosis is inhibited by addition of one or two residues to the sybII C terminus depending on their energy of transfer from water to the membrane interface, following a Boltzmann distribution. These results suggest that following stimulation, the SNARE complex pulls the C terminus of sybII deeper into the vesicle membrane. We propose that this movement disrupts the vesicular membrane continuity leading to fusion pore formation. In contrast to current models, the experiments suggest that fusion pore formation begins with molecular rearrangements at the intravesicular membrane leaflet and not between the apposed cytoplasmic leaflets.

PMID:
20937897
PMCID:
PMC2972926
DOI:
10.1073/pnas.1006727107
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center