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Distinct domains of complexin I differentially regulate neurotransmitter release

2007; Nature Portfolio; Volume: 14; Issue: 10 Linguagem: Inglês

10.1038/nsmb1292

1545-9993

Mingshan Xue, Kerstin Reim, Xiaocheng Chen, Hsiao‐Tuan Chao, Hui Deng, Josep Rizo, Nils Brose, Christian Rosenmund,

Lipid Membrane Structure and Behavior

Complexins constitute a family of four synaptic high-affinity SNARE complex–binding proteins. They positively regulate a late, post-priming step in Ca2+-triggered synchronous neurotransmitter release, but the underlying molecular mechanisms are unclear. We show here that SNARE complex binding of complexin I (CplxI) via its central α-helix is necessary but, unexpectedly, not sufficient for its key function in promoting neurotransmitter release. An accessory α-helix on the N-terminal side of the SNARE complex–binding region has an inhibitory effect on fast synaptic exocytosis, whereas sequences N-terminally adjacent to this helix facilitate Ca2+-triggered release even in the absence of the Ca2+ sensor synaptotagmin-1. Our results indicate that distinct functional domains of CplxI differentially regulate synaptic exocytosis and that, through the interplay between these domains, CplxI carries out a crucial role in fine-tuning Ca2+-triggered fast neurotransmitter release.