Distinct domains of complexin I differentially regulate neurotransmitter release.
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 alpha-helix is necessary but, unexpectedly, not sufficient for its key function in promoting neurotransmitter release. An accessory alpha-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.
Xue
Mingshan
M
Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
Reim
Kerstin
K
Chen
Xiaocheng
X
Chao
Hsiao-Tuan
HT
Deng
Hui
H
Rizo
Josep
J
Brose
Nils
N
Rosenmund
Christian
C
D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D050863:Synaptotagmin I / Q000378:metabolism