Abstract
Ca2+ binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca2+-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca2+ binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca2+-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca2+-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca2+-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca2+-triggered neurotransmitter release.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1175-1187 |
| Number of pages | 13 |
| Journal | Cell |
| Volume | 126 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 22 2006 |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
Cite this
A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis. / Tang, Jiong; Maximov, Anton; Shin, Ok Ho; Dai, Han; Rizo-Rey, Jose; Südhof, Thomas C.
In: Cell, Vol. 126, No. 6, 22.09.2006, p. 1175-1187.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A Complexin/Synaptotagmin 1 Switch Controls Fast Synaptic Vesicle Exocytosis
AU - Tang, Jiong
AU - Maximov, Anton
AU - Shin, Ok Ho
AU - Dai, Han
AU - Rizo-Rey, Jose
AU - Südhof, Thomas C.
PY - 2006/9/22
Y1 - 2006/9/22
N2 - Ca2+ binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca2+-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca2+ binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca2+-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca2+-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca2+-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca2+-triggered neurotransmitter release.
AB - Ca2+ binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca2+-triggered exocytosis requires complexins. Synaptotagmin 1 and complexins both bind to assembled SNARE complexes, but it is unclear how their functions are coupled. Here we propose that complexin binding activates SNARE complexes into a metastable state and that Ca2+ binding to synaptotagmin 1 triggers fast exocytosis by displacing complexin from metastable SNARE complexes. Specifically, we demonstrate that, biochemically, synaptotagmin 1 competes with complexin for SNARE-complex binding, thereby dislodging complexin from SNARE complexes in a Ca2+-dependent manner. Physiologically, increasing the local concentration of complexin selectively impairs fast Ca2+-triggered exocytosis but retains other forms of SNARE-dependent fusion. The hypothesis that Ca2+-induced displacement of complexins from SNARE complexes triggers fast exocytosis accounts for the loss-of-function and gain-of-function phenotypes of complexins and provides a molecular explanation for the high speed and synchronicity of fast Ca2+-triggered neurotransmitter release.
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UR - http://www.scopus.com/inward/citedby.url?scp=33748605056&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2006.08.030
DO - 10.1016/j.cell.2006.08.030
M3 - Article
C2 - 16990140
AN - SCOPUS:33748605056
VL - 126
SP - 1175
EP - 1187
JO - Cell
JF - Cell
SN - 0092-8674
IS - 6
ER -