Distinct domains of complexin I differentially regulate neurotransmitter release

M Xue, K Reim, X Chen, HT Chao, H Deng… - Nature structural & …, 2007 - nature.com
M Xue, K Reim, X Chen, HT Chao, H Deng, J Rizo, N Brose, C Rosenmund
Nature structural & molecular biology, 2007nature.com
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 …
Abstract
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.
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