| First Author | Yang X | Year | 2010 |
| Journal | Neuron | Volume | 68 |
| Issue | 5 | Pages | 907-20 |
| PubMed ID | 21145004 | Mgi Jnum | J:167741 |
| Mgi Id | MGI:4879064 | Doi | 10.1016/j.neuron.2010.11.001 |
| Citation | Yang X, et al. (2010) Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory alpha helix. Neuron 68(5):907-20 |
| abstractText | 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 alpha helix, respectively. Mutations designed to test whether the accessory alpha helix of complexin clamps exocytosis by inserting into SNARE-complexes support this hypothesis, suggesting that the accessory alpha 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. |
