Comparative analysis of Drosophila and mammalian complexins as fusion clamps and facilitators of neurotransmitter release
Name
Cho et al., 2010.pdf
Description
main article
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2.81 MB
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1ce746455a04382b4aecb108732e027c
Author(s)
Cho, Richard W.
Song, Yun
Littleton, J. Troy
Date Issued
July 2010
Journal
Molecular and Cellular Neuroscience
Publisher
Elsevier B.V.
Citation
Cho, Richard W., Yun Song, and J. Troy Littleton. “Comparative Analysis of Drosophila and Mammalian Complexins as Fusion Clamps and Facilitators of Neurotransmitter Release.” Molecular and Cellular Neuroscience 45, no. 4 (December 2010): 389-397.
Version
Author's final manuscript
Abstract
The SNARE-binding protein complexin (Cpx) has been demonstrated to regulate synaptic vesicle fusion. Previous studies are consistent with Cpx functioning either as a synaptic vesicle fusion clamp to prevent premature exocytosis, or as a facilitator to directly stimulate release. Here we examined conserved roles of invertebrate and mammalian Cpx isoforms in the regulation of neurotransmitter release using the Drosophila neuromuscular junction as a model synapse. We find that SNARE binding by Cpx is required for its role as a fusion clamp. All four mammalian Cpx proteins (mCpx), which have been demonstrated to facilitate release, also function as fusion clamps when expressed in Drosophila cpx null mutants, though their clamping abilities vary between isoforms. Moreover, expression of mCpx I, II or III isoforms dramatically enhance evoked release compared to mCpx IV or Drosophila Cpx. Differences in the clamping and facilitating properties of complexin isoforms can be partially attributed to differences in the C-terminal membrane tethering domain. Our findings indicate that the function of complexins as fusion clamps and facilitators of fusion are conserved across evolution, and that these roles are genetically separable within an isoform and across different isoforms.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.mcn.2010.07.012
