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PMID: 20937897 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Role of the synaptobrevin C terminus in fusion pore formation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 43 ·2010-10-26 ·Pages 18463-8

Ngatchou AN, Kisler K, Fang Q, Walter AM, Zhao Y, Bruns D, Sørensen JB, Lindau M

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.

MeSH Terms
Amino Acid Sequence Animals Biophysical Phenomena Cells, Cultured Chromaffin Cells/physiology Exocytosis/physiology In Vitro Techniques Membrane Fusion/physiology Mice Mice, Knockout Models, Neurological Molecular Sequence Data Mutant Proteins/chemistry,genetics,physiology Neurotransmitter Agents/metabolism Rats Recombinant Fusion Proteins/chemistry,genetics,metabolism Thermodynamics Vesicle-Associated Membrane Protein 2/chemistry,genetics,physiology
Chemicals
Mutant Proteins Neurotransmitter Agents Recombinant Fusion Proteins Vamp2 protein, rat Vesicle-Associated Membrane Protein 2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Ngatchou Annita N
School of Applied and Engineering Physics, 212 Clark Hall, Cornell University, Ithaca, NY 14853, USA.
Kisler Kassandra
Fang Qinghua
Walter Alexander M
Zhao Ying
Bruns Dieter
Sørensen Jakob B
Lindau Manfred
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1006727107
Published
2010-10-26
Epub
2010-00-11
Pages
18463-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2972926
Subset
IM
Grants
NINDS NIH HHS · R01 NS038200-08 · United States
NINDS NIH HHS · R01 NS038200 · United States
NIGMS NIH HHS · T32GM008267 · United States
NIGMS NIH HHS · R01GM085808 · United States
NIGMS NIH HHS · R01 GM085808-10 · United States
NIGMS NIH HHS · R01 GM085808-09 · United States
NIGMS NIH HHS · R01 GM085808-10S1 · United States
NIGMS NIH HHS · R01 GM085808 · United States
NINDS NIH HHS · R01NS38200 · United States
NIGMS NIH HHS · T32 GM008267 · United States
External Links
PubMed source DOI: 10.1073/pnas.1006727107 PMC Full Text View journal details
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