TY - JOUR
T1 - Distinct domains of complexin I differentially regulate neurotransmitter release
AU - Xue, Mingshan
AU - Reim, Kerstin
AU - Chen, Xiaocheng
AU - Chao, Hsiao Tuan
AU - Deng, Hui
AU - Rizo-Rey, Jose
AU - Brose, Nils
AU - Rosenmund, Christian
N1 - Funding Information:
We thank H. Chen, T. Hellmann, I. Herfort, D. Reuter, S. Wenger and A. Zeuch for excellent technical assistance; F. Benseler, D. Schwerdtfeger and I. Thanhäuser for DNA sequencing and oligonucleotide synthesis; R. Nehring and R. Atkinson for technical advice; H. Bellen for comments on the manuscript and E. Neher for continuous support and advice. This work was supported by the Deutsche Forschungsgemeinschaft (SFB 523/B9 to N.B. and C.R.), a Heisenberg Fellowship (to C.R.), the Brown Foundation (to C.R.), the US National Institutes of Health (NS50655 to C.R., NS37200 to J.R.) and Baylor Research Advocates for Student Scientists and a McNair Fellowship (both to H.-T.C.).
PY - 2007/10
Y1 - 2007/10
N2 - 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 Ca 2+-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.
AB - 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 Ca 2+-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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U2 - 10.1038/nsmb1292
DO - 10.1038/nsmb1292
M3 - Article
C2 - 17828276
AN - SCOPUS:34948901461
SN - 1545-9993
VL - 14
SP - 949
EP - 958
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 10
ER -