Complexin Clamps Asynchronous Release by Blocking a Secondary Ca2+ Sensor via Its Accessory α Helix

Xiaofei Yang, Yea Jin Kaeser-Woo, Zhiping P. Pang, Wei Xu, Thomas C. Südhof

Research output: Contribution to journalArticle

103 Citations (Scopus)

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 Ca2+ 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 Ca2+ sensor. Activation and clamping functions of complexin depend on distinct, autonomously acting sequences, namely its N-terminal region and accessory α helix, respectively. Mutations designed to test whether the accessory α helix of complexin clamps exocytosis by inserting into SNARE-complexes support this hypothesis, suggesting that the accessory α helix blocks completion of trans-SNARE-complex assembly until Ca2+ 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 Ca2+ sensor. Thus, complexin performs mechanistically distinct activation and clamping functions that operate in conjunction with synaptotagmin-1 by controlling trans-SNARE-complex assembly.

Original languageEnglish (US)
Pages (from-to)907-920
Number of pages14
JournalNeuron
Volume68
Issue number5
DOIs
StatePublished - Dec 9 2010

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SNARE Proteins
Synaptotagmin I
Exocytosis
Synaptic Vesicles
Constriction
Vesicle-Associated Membrane Protein 2
Synaptotagmins
Mutation
Neurotransmitter Agents
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Complexin Clamps Asynchronous Release by Blocking a Secondary Ca2+ Sensor via Its Accessory α Helix. / Yang, Xiaofei; Kaeser-Woo, Yea Jin; Pang, Zhiping P.; Xu, Wei; Südhof, Thomas C.

In: Neuron, Vol. 68, No. 5, 09.12.2010, p. 907-920.

Research output: Contribution to journalArticle

Yang, Xiaofei ; Kaeser-Woo, Yea Jin ; Pang, Zhiping P. ; Xu, Wei ; Südhof, Thomas C. / Complexin Clamps Asynchronous Release by Blocking a Secondary Ca2+ Sensor via Its Accessory α Helix. In: Neuron. 2010 ; Vol. 68, No. 5. pp. 907-920.
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