title: Distinct domains of complexin I differentially regulate neurotransmitter release.
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 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.
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Mingshan
authors.initials: M
authors.lastname: Xue
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reim
authors.forename: Xiaocheng
authors.initials: X
authors.lastname: Chen
authors.forename: Hsiao-Tuan
authors.initials: HT
authors.lastname: Chao
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Josep
authors.initials: J
authors.lastname: Rizo
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Christian
authors.initials: C
authors.lastname: Rosenmund
mesh_terms: 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