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Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis

The synaptic SNARE complex is a highly stable four-helix bundle that links the vesicle and plasma membranes and plays an essential role in the Ca(2+)-triggered release of neurotransmitters and hormones. An understanding has yet to be achieved of how this complex assembles and undergoes structural tr...

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Detalles Bibliográficos
Autores principales: Han, Xue, Jackson, Meyer B.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063557/
https://www.ncbi.nlm.nih.gov/pubmed/16418536
http://dx.doi.org/10.1083/jcb.200510012
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author Han, Xue
Jackson, Meyer B.
author_facet Han, Xue
Jackson, Meyer B.
author_sort Han, Xue
collection PubMed
description The synaptic SNARE complex is a highly stable four-helix bundle that links the vesicle and plasma membranes and plays an essential role in the Ca(2+)-triggered release of neurotransmitters and hormones. An understanding has yet to be achieved of how this complex assembles and undergoes structural transitions during exocytosis. To investigate this question, we have mutated residues within the hydrophobic core of the SNARE complex along the entire length of all four chains and examined the consequences using amperometry to measure fusion pore opening and dilation. Mutations throughout the SNARE complex reduced two distinct rate processes before fusion pore opening to different degrees. These results suggest that two distinct, fully assembled conformations of the SNARE complex drive transitions leading to open fusion pores. In contrast, a smaller number of mutations that were scattered through the SNARE complex but were somewhat concentrated in the membrane-distal half stabilized open fusion pores. These results suggest that a structural transition within a partially disassembled complex drives the dilation of open fusion pores. The dependence of these three rate processes on position within the SNARE complex does not support vectorial SNARE complex zipping during exocytosis.
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spelling pubmed-20635572008-03-19 Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis Han, Xue Jackson, Meyer B. J Cell Biol Research Articles The synaptic SNARE complex is a highly stable four-helix bundle that links the vesicle and plasma membranes and plays an essential role in the Ca(2+)-triggered release of neurotransmitters and hormones. An understanding has yet to be achieved of how this complex assembles and undergoes structural transitions during exocytosis. To investigate this question, we have mutated residues within the hydrophobic core of the SNARE complex along the entire length of all four chains and examined the consequences using amperometry to measure fusion pore opening and dilation. Mutations throughout the SNARE complex reduced two distinct rate processes before fusion pore opening to different degrees. These results suggest that two distinct, fully assembled conformations of the SNARE complex drive transitions leading to open fusion pores. In contrast, a smaller number of mutations that were scattered through the SNARE complex but were somewhat concentrated in the membrane-distal half stabilized open fusion pores. These results suggest that a structural transition within a partially disassembled complex drives the dilation of open fusion pores. The dependence of these three rate processes on position within the SNARE complex does not support vectorial SNARE complex zipping during exocytosis. The Rockefeller University Press 2006-01-16 /pmc/articles/PMC2063557/ /pubmed/16418536 http://dx.doi.org/10.1083/jcb.200510012 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Han, Xue
Jackson, Meyer B.
Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title_full Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title_fullStr Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title_full_unstemmed Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title_short Structural transitions in the synaptic SNARE complex during Ca(2+)-triggered exocytosis
title_sort structural transitions in the synaptic snare complex during ca(2+)-triggered exocytosis
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063557/
https://www.ncbi.nlm.nih.gov/pubmed/16418536
http://dx.doi.org/10.1083/jcb.200510012
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