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Publication : Role of the synaptobrevin C terminus in fusion pore formation.

First Author  Ngatchou AN Year  2010
Journal  Proc Natl Acad Sci U S A Volume  107
Issue  43 Pages  18463-8
PubMed ID  20937897 Mgi Jnum  J:165505
Mgi Id  MGI:4837581 Doi  10.1073/pnas.1006727107
Citation  Ngatchou AN, et al. (2010) Role of the synaptobrevin C terminus in fusion pore formation. Proc Natl Acad Sci U S A 107(43):18463-8
abstractText  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.
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