Complexin arrests a pool of docked vesicles for fast Ca2+-dependent release
- PMID: 22705946
- PMCID: PMC3411073
- DOI: 10.1038/emboj.2012.164
Complexin arrests a pool of docked vesicles for fast Ca2+-dependent release
Abstract
Regulated exocytosis requires that the assembly of the basic membrane fusion machinery is temporarily arrested. Synchronized membrane fusion is then caused by a specific trigger--a local rise of the Ca(2+) concentration. Using reconstituted giant unilamellar vesicles (GUVs), we have analysed the role of complexin and membrane-anchored synaptotagmin 1 in arresting and synchronizing fusion by lipid-mixing and cryo-electron microscopy. We find that they mediate the formation and consumption of docked small unilamellar vesicles (SUVs) via the following sequence of events: Synaptotagmin 1 mediates v-SNARE-SUV docking to t-SNARE-GUVs in a Ca(2+)-independent manner. Complexin blocks vesicle consumption, causing accumulation of docked vesicles. Together with synaptotagmin 1, complexin synchronizes and stimulates rapid fusion of accumulated docked vesicles in response to physiological Ca(2+) concentrations. Thus, the reconstituted assay resolves both the stimulatory and inhibitory function of complexin and mimics key aspects of synaptic vesicle fusion.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Figures
Similar articles
-
Complexin inhibits spontaneous release and synchronizes Ca2+-triggered synaptic vesicle fusion by distinct mechanisms.Elife. 2014 Aug 13;3:e03756. doi: 10.7554/eLife.03756. Elife. 2014. PMID: 25122624 Free PMC article.
-
Synergistic roles of Synaptotagmin-1 and complexin in calcium-regulated neuronal exocytosis.Elife. 2020 May 13;9:e54506. doi: 10.7554/eLife.54506. Elife. 2020. PMID: 32401194 Free PMC article.
-
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
-
Complexins: small but capable.Cell Mol Life Sci. 2015 Nov;72(22):4221-35. doi: 10.1007/s00018-015-1998-8. Epub 2015 Aug 6. Cell Mol Life Sci. 2015. PMID: 26245303 Free PMC article. Review.
-
Putting the clamps on membrane fusion: how complexin sets the stage for calcium-mediated exocytosis.FEBS Lett. 2007 May 22;581(11):2131-9. doi: 10.1016/j.febslet.2007.02.066. Epub 2007 Mar 5. FEBS Lett. 2007. PMID: 17350005 Review.
Cited by
-
Complexin facilitates exocytosis and synchronizes vesicle release in two secretory model systems.J Physiol. 2013 May 15;591(10):2463-73. doi: 10.1113/jphysiol.2012.244517. Epub 2013 Feb 11. J Physiol. 2013. PMID: 23401610 Free PMC article.
-
Re-examining how complexin inhibits neurotransmitter release.Elife. 2014 May 8;3:e02391. doi: 10.7554/eLife.02391. Elife. 2014. PMID: 24842998 Free PMC article.
-
The blockade of the neurotransmitter release apparatus by botulinum neurotoxins.Cell Mol Life Sci. 2014 Mar;71(5):793-811. doi: 10.1007/s00018-013-1380-7. Epub 2013 Jun 11. Cell Mol Life Sci. 2014. PMID: 23749048 Free PMC article. Review.
-
Structural basis for the clamping and Ca2+ activation of SNARE-mediated fusion by synaptotagmin.Nat Commun. 2019 Jun 3;10(1):2413. doi: 10.1038/s41467-019-10391-x. Nat Commun. 2019. PMID: 31160571 Free PMC article.
-
A Programmable DNA Origami Platform to Organize SNAREs for Membrane Fusion.J Am Chem Soc. 2016 Apr 6;138(13):4439-47. doi: 10.1021/jacs.5b13107. Epub 2016 Mar 23. J Am Chem Soc. 2016. PMID: 26938705 Free PMC article.
References
-
- Bai J, Tucker WC, Chapman ER (2004) PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane. Nat Struct Mol Biol 11: 36–44 - PubMed
-
- Begemann M, Grube S, Papiol S, Malzahn D, Krampe H, Ribbe K, Friedrichs H, Radyushkin KA, El-Kordi A, Benseler F, Hannke K, Sperling S, Schwerdtfeger D, Thanhauser I, Gerchen MF, Ghorbani M, Gutwinski S, Hilmes C, Leppert R, Ronnenberg A et al. (2010) Modification of cognitive performance in schizophrenia by complexin 2 gene polymorphisms. Arch Gen Psychiatry 67: 879–888 - PubMed
-
- Bruns D, Jahn R (1995) Real-time measurement of transmitter release from single synaptic vesicles. Nature 377: 62–65 - PubMed
-
- Chapman ER (2008) How does synaptotagmin trigger neurotransmitter release? Annu Rev Biochem 77: 615–641 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous
