Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity
- PMID: 20400951
- PMCID: PMC3172005
- DOI: 10.1038/nsmb.1791
Binding of the complexin N terminus to the SNARE complex potentiates synaptic-vesicle fusogenicity
Abstract
Complexins facilitate and inhibit neurotransmitter release through distinct domains, and their function was proposed to be coupled to the Ca(2+) sensor synaptotagmin-1 (Syt1). However, the mechanisms underlying complexin function remain unclear. We now uncover an interaction between the complexin N terminus and the SNARE complex C terminus, and we show that disrupting this interaction abolishes the facilitatory function of complexins in mouse neurons. Analyses of hypertonically induced exocytosis show that complexins enhance synaptic-vesicle fusogenicity. Genetic experiments crossing complexin- and Syt1-null mice indicate a functional interaction between these proteins but also show that complexins can promote Ca(2+)-triggered release in the absence of Syt1. We propose that the complexin N terminus stabilizes the SNARE complex C terminus and/or helps release the inhibitory function of complexins, thereby activating the fusion machinery in a manner that may cooperate with Syt1 but does not require Syt1.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0001.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0002.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0003.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0004.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0005.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0006.gif)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0007.gif)
![Figure 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3172005/bin/nihms-315682-f0008.gif)
Similar articles
-
Models of synaptotagmin-1 to trigger Ca2+ -dependent vesicle fusion.FEBS Lett. 2018 Nov;592(21):3480-3492. doi: 10.1002/1873-3468.13193. Epub 2018 Jul 30. FEBS Lett. 2018. PMID: 30004579 Review.
-
The primed SNARE-complexin-synaptotagmin complex for neuronal exocytosis.Nature. 2017 Aug 24;548(7668):420-425. doi: 10.1038/nature23484. Epub 2017 Aug 16. Nature. 2017. PMID: 28813412 Free PMC article.
-
C-terminal complexin sequence is selectively required for clamping and priming but not for Ca2+ triggering of synaptic exocytosis.J Neurosci. 2012 Feb 22;32(8):2877-85. doi: 10.1523/JNEUROSCI.3360-11.2012. J Neurosci. 2012. PMID: 22357870 Free PMC article.
-
For better or for worse: complexins regulate SNARE function and vesicle fusion.Traffic. 2008 Sep;9(9):1403-13. doi: 10.1111/j.1600-0854.2008.00758.x. Epub 2008 Apr 28. Traffic. 2008. PMID: 18445121 Review.
-
A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.Cell. 2006 Sep 22;126(6):1175-87. doi: 10.1016/j.cell.2006.08.030. Cell. 2006. PMID: 16990140
Cited by
-
Complexin has a dual synaptic function as checkpoint protein in vesicle priming and as a promoter of vesicle fusion.Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2320505121. doi: 10.1073/pnas.2320505121. Epub 2024 Apr 3. Proc Natl Acad Sci U S A. 2024. PMID: 38568977 Free PMC article.
-
Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes.Nat Commun. 2024 Mar 26;15(1):2652. doi: 10.1038/s41467-024-46828-1. Nat Commun. 2024. PMID: 38531902 Free PMC article.
-
Light-dependent regulation of neurotransmitter release from rod photoreceptor ribbon synapses involves an interplay of Complexin 4 and Transducin with the SNARE complex.Front Mol Neurosci. 2024 Feb 28;17:1308466. doi: 10.3389/fnmol.2024.1308466. eCollection 2024. Front Mol Neurosci. 2024. PMID: 38481472 Free PMC article.
-
Regulation of Syntaxin3B-Mediated Membrane Fusion by T14, Munc18, and Complexin.Biomolecules. 2023 Sep 28;13(10):1463. doi: 10.3390/biom13101463. Biomolecules. 2023. PMID: 37892145 Free PMC article.
-
Complexins: Ubiquitously Expressed Presynaptic Regulators of SNARE-Mediated Synaptic Vesicle Fusion.Adv Neurobiol. 2023;33:255-285. doi: 10.1007/978-3-031-34229-5_10. Adv Neurobiol. 2023. PMID: 37615870
References
-
- Jahn R, Scheller RH. SNAREs - engines for membrane fusion. Nat Rev Mol Cell Biol. 2006;7:631–43. - PubMed
-
- Wojcik SM, Brose N. Regulation of membrane fusion in synaptic excitation-secretion coupling: speed and accuracy matter. Neuron. 2007;55:11–24. - PubMed
-
- McMahon HT, Missler M, Li C, Sudhof TC. Complexins: cytosolic proteins that regulate SNAP receptor function. Cell. 1995;83:111–9. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous