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Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory ? helix.


ABSTRACT: Complexin activates and clamps neurotransmitter release; impairing complexin function decreases synchronous, but increases spontaneous and asynchronous synaptic vesicle exocytosis. Here, we show that complexin-different from the Ca(2+) sensor synaptotagmin-1-activates synchronous exocytosis by promoting synaptic vesicle priming, but clamps spontaneous and asynchronous exocytosis-similar to synaptotagmin-1-by blocking a secondary Ca(2+) sensor. Activation and clamping functions of complexin depend on distinct, autonomously acting sequences, namely its N-terminal region and accessory ? helix, respectively. Mutations designed to test whether the accessory ? helix of complexin clamps exocytosis by inserting into SNARE-complexes support this hypothesis, suggesting that the accessory ? helix blocks completion of trans-SNARE-complex assembly until Ca(2+) binding to synaptotagmin relieves this block. Moreover, a juxtamembranous mutation in the SNARE-protein synaptobrevin-2, which presumably impairs force transfer from nascent trans-SNARE complexes onto fusing membranes, also unclamps spontaneous fusion by disinhibiting a secondary Ca(2+) sensor. Thus, complexin performs mechanistically distinct activation and clamping functions that operate in conjunction with synaptotagmin-1 by controlling trans-SNARE-complex assembly.

SUBMITTER: Yang X 

PROVIDER: S-EPMC3050570 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory α helix.

Yang Xiaofei X   Kaeser-Woo Yea Jin YJ   Pang Zhiping P ZP   Xu Wei W   Südhof Thomas C TC  

Neuron 20101201 5


Complexin activates and clamps neurotransmitter release; impairing complexin function decreases synchronous, but increases spontaneous and asynchronous synaptic vesicle exocytosis. Here, we show that complexin-different from the Ca(2+) sensor synaptotagmin-1-activates synchronous exocytosis by promoting synaptic vesicle priming, but clamps spontaneous and asynchronous exocytosis-similar to synaptotagmin-1-by blocking a secondary Ca(2+) sensor. Activation and clamping functions of complexin depen  ...[more]

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