Mechanisms of SNARE proteins in membrane fusion.


Journal

Nature reviews. Molecular cell biology
ISSN: 1471-0080
Titre abrégé: Nat Rev Mol Cell Biol
Pays: England
ID NLM: 100962782

Informations de publication

Date de publication:
17 Oct 2023
Historique:
accepted: 06 09 2023
medline: 18 10 2023
pubmed: 18 10 2023
entrez: 17 10 2023
Statut: aheadofprint

Résumé

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are a family of small conserved eukaryotic proteins that mediate membrane fusion between organelles and with the plasma membrane. SNAREs are directly or indirectly anchored to membranes. Prior to fusion, complementary SNAREs assemble between membranes with the aid of accessory proteins that provide a scaffold to initiate SNARE zippering, pulling the membranes together and mediating fusion. Recent advances have enabled the construction of detailed models describing bilayer transitions and energy barriers along the fusion pathway and have elucidated the structures of SNAREs complexed in various states with regulatory proteins. In this Review, we discuss how these advances are yielding an increasingly detailed picture of the SNARE-mediated fusion pathway, leading from first contact between the membranes via metastable non-bilayer intermediates towards the opening and expansion of a fusion pore. We describe how SNARE proteins assemble into complexes, how this assembly is regulated by accessory proteins and how SNARE complexes overcome the free energy barriers that prevent spontaneous membrane fusion.

Identifiants

pubmed: 37848589
doi: 10.1038/s41580-023-00668-x
pii: 10.1038/s41580-023-00668-x
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2023. Springer Nature Limited.

Références

Kalia, R. & Frost, A. Open and cut: allosteric motion and membrane fission by dynamin superfamily proteins. Mol. Biol. Cell 30, 2097–2104 (2019).
pubmed: 31365329 pmcid: 6743466 doi: 10.1091/mbc.E16-10-0709
Pfitzner, A. K., von Filseck, J. M. & Roux, A. Principles of membrane remodeling by dynamic ESCRT-III polymers. Trends Cell Biol. 31, 856–868 (2021).
pubmed: 33980463 doi: 10.1016/j.tcb.2021.04.005
Westermann, B. Mitochondrial fusion and fission in cell life and death. Nat. Rev. Mol. Cell Biol. 11, 872–884 (2010).
pubmed: 21102612 doi: 10.1038/nrm3013
Harrison, S. C. Viral membrane fusion. Virology 479, 498–507 (2015).
pubmed: 25866377 doi: 10.1016/j.virol.2015.03.043
White, J. M., Ward., A.E., Odongo, L. & Tamm, L.K. Viral membrane fusion: a dance between proteins and lipids. Annu. Rev. Virol. 10, https://doi.org/10.1146/annurev-virology-111821-093413 (2023).
Söllner, T. et al. SNAP receptors implicated in vesicle targeting and fusion. Nature 362, 318–324 (1993).
pubmed: 8455717 doi: 10.1038/362318a0
Südhof, T. C. & Rothman, J. E. Membrane fusion: grappling with SNARE and SM proteins. Science 323, 474–477 (2009).
pubmed: 19164740 pmcid: 3736821 doi: 10.1126/science.1161748
Südhof, T. C. The synaptic vesicle cycle. Annu. Rev. Neurosci. 27, 509–547 (2004).
pubmed: 15217342 doi: 10.1146/annurev.neuro.26.041002.131412
Schillemans, M., Karampini, E., Kat, M. & Bierings, R. Exocytosis of Weibel–Palade bodies: how to unpack a vascular emergency kit. J. Thromb. Haemost. 17, 6–18 (2019).
pubmed: 30375718 doi: 10.1111/jth.14322
Jahn, R. & Scheller, R. H. SNAREs—engines for membrane fusion. Nat. Rev. Mol. Cell Biol. 7, 631–643 (2006).
pubmed: 16912714 doi: 10.1038/nrm2002
Brukman, N. G., Uygur, B., Podbilewicz, B. & Chernomordik, L. V. How cells fuse. J. Cell Biol. 218, 1436–1451 (2019).
pubmed: 30936162 pmcid: 6504885 doi: 10.1083/jcb.201901017
Petrany, M. J. & Millay, D. P. Cell fusion: merging membranes and making muscle. Trends Cell Biol. 29, 964–973 (2019).
pubmed: 31648852 pmcid: 7849503 doi: 10.1016/j.tcb.2019.09.002
Gao, S. & Hu, J. Mitochondrial fusion: the machineries in and out. Trends Cell Biol. 31, 62–74 (2021).
pubmed: 33092941 doi: 10.1016/j.tcb.2020.09.008
Wickner, W. & Rizo, J. A cascade of multiple proteins and lipids catalyzes membrane fusion. Mol. Biol. Cell 28, 707–711 (2017).
pubmed: 28292915 pmcid: 5349777 doi: 10.1091/mbc.e16-07-0517
Zhang, Y. & Hughson, F. M. Chaperoning SNARE folding and assembly. Annu. Rev. Biochem. 90, 581–603 (2021).
pubmed: 33823650 pmcid: 8900292 doi: 10.1146/annurev-biochem-081820-103615
Rizo, J. Molecular mechanisms underlying neurotransmitter release. Annu. Rev. Biophys. 51, 377–408 (2022).
pubmed: 35167762 pmcid: 9490555 doi: 10.1146/annurev-biophys-111821-104732
Brunger, A. T., Choi, U. B., Lai, Y., Leitz, J. & Zhou, Q. Molecular mechanisms of fast neurotransmitter release. Annu. Rev. Biophys. 47, 469–497 (2018).
pubmed: 29792815 pmcid: 6378885 doi: 10.1146/annurev-biophys-070816-034117
Bubnis, G. & Grubmüller, H. Sequential water and headgroup merger: membrane poration paths and energetics from MD simulations. Biophys. J. 119, 2418–2430 (2020).
pubmed: 33189685 pmcid: 7822740 doi: 10.1016/j.bpj.2020.10.037
Smirnova, Y. G., Risselada, H. J. & Müller, M. Thermodynamically reversible paths of the first fusion intermediate reveal an important role for membrane anchors of fusion proteins. Proc. Natl Acad. Sci. USA 116, 2571–2576 (2019).
pubmed: 30700547 pmcid: 6377489 doi: 10.1073/pnas.1818200116
Kozlov, M. M. & Markin, V. S. Possible mechanism of membrane fusion [Russian]. Biofizika 28, 242–247 (1983).
pubmed: 6849992
Kuzmin, P. I., Zimmerberg, J., Chizmadzhev, Y. A. & Cohen, F. S. A quantitative model for membrane fusion based on low-energy intermediates. Proc. Natl Acad. Sci. USA 98, 7235–7240 (2001).
pubmed: 11404463 pmcid: 34652 doi: 10.1073/pnas.121191898
Kozlov, M. M. & Chernomordik, L. V. Membrane tension and membrane fusion. Curr. Opin. Struct. Biol. 33, 61–67 (2015).
pubmed: 26282924 pmcid: 4641764 doi: 10.1016/j.sbi.2015.07.010
Chernomordik, L. V. & Kozlov, M. M. Protein–lipid interplay in fusion and fission of biological membranes. Annu. Rev. Biochem 72, 175–207 (2003).
pubmed: 14527322 doi: 10.1146/annurev.biochem.72.121801.161504
Cohen, F. S. & Melikyan, G. B. The energetics of membrane fusion from binding, through hemifusion, pore formation, and pore enlargement. J. Membr. Biol. 199, 1–14 (2004).
pubmed: 15366419 doi: 10.1007/s00232-004-0669-8
Fan, Z. A., Tsang, K. Y., Chen, S. H. & Chen, Y. F. Revisit the correlation between the elastic mechanics and fusion of lipid membranes. Sci. Rep. 6, 31470 (2016).
pubmed: 27534263 pmcid: 4989284 doi: 10.1038/srep31470
Chernomordik, L. V. & Kozlov, M. M. Mechanics of membrane fusion. Nat. Struct. Mol. Biol. 15, 675–683 (2008).
pubmed: 18596814 pmcid: 2548310 doi: 10.1038/nsmb.1455
Marrink, S. J. & Mark, A. E. The mechanism of vesicle fusion as revealed by molecular dynamics simulations. J. Am. Chem. Soc. 125, 11144–11145 (2003).
pubmed: 16220905 doi: 10.1021/ja036138+
Beaven, A. H., Sapp, K. & Sodt, A. J. Simulated dynamic cholesterol redistribution favors membrane fusion pore constriction. Biophys. J. 122, 2162–2175 (2022).
pubmed: 36588341 doi: 10.1016/j.bpj.2022.12.024
Johner, N., Harries, D. & Khelashvili, G. Implementation of a methodology for determining elastic properties of lipid assemblies from molecular dynamics simulations. BMC Bioinform. 17, 161 (2016).
doi: 10.1186/s12859-016-1003-z
Rice, A., Zimmerberg, J. & Pastor, R. W. Initiation and evolution of pores formed by influenza fusion peptides probed by lysolipid inclusion. Biophys. J. 122, 1018–1032 (2023).
pubmed: 36575795 doi: 10.1016/j.bpj.2022.12.029
Grafmuller, A., Shillcock, J. & Lipowsky, R. The fusion of membranes and vesicles: pathway and energy barriers from dissipative particle dynamics. Biophys. J. 96, 2658–2675 (2009).
pubmed: 19348749 pmcid: 2711276 doi: 10.1016/j.bpj.2008.11.073
Kawamoto, S., Klein, M. L. & Shinoda, W. Coarse-grained molecular dynamics study of membrane fusion: curvature effects on free energy barriers along the stalk mechanism. J. Chem. Phys. 143, 243112 (2015).
pubmed: 26723597 doi: 10.1063/1.4933087
McLaughlin, S. The electrostatic properties of membranes. Annu. Rev. Biophys. Biophys. Chem. 18, 113–136 (1989).
pubmed: 2660821 doi: 10.1146/annurev.bb.18.060189.000553
Lipowsky, R. The conformation of membranes. Nature 349, 475–481 (1991).
pubmed: 1992351 doi: 10.1038/349475a0
Rand, R. P. & Parsegian, V. A. Physical force considerations in model and biological membranes. Can. J. Biochem. Cell Biol. 62, 752–759 (1984).
pubmed: 6498591 doi: 10.1139/o84-097
Israelachvili, J. N. Surface forces. In The Handbook of Surface Imaging and Visualization (ed. Hubbard, A. T.) Ch. 24, 793–817 (Taylor & Francis, 1995).
Tamm, L. K. & Han, X. Viral fusion peptides: a tool set to disrupt and connect biological membranes. Biosci. Rep. 20, 501–518 (2000).
pubmed: 11426691 doi: 10.1023/A:1010406920417
Risselada, H. J. et al. Line-tension controlled mechanism for influenza fusion. PLoS ONE 7, e38302 (2012).
pubmed: 22761674 pmcid: 3386277 doi: 10.1371/journal.pone.0038302
Langosch, D. et al. Peptide mimics of SNARE transmembrane segments drive membrane fusion depending on their conformational plasticity. J. Mol. Biol. 311, 709–721 (2001).
pubmed: 11518525 doi: 10.1006/jmbi.2001.4889
Hernandez, J. M., Kreutzberger, A. J. B., Kiessling, V., Tamm, L. K. & Jahn, R. Variable cooperativity in SNARE-mediated membrane fusion. Proc. Natl Acad. Sci. USA 111, 12037–12042 (2014).
pubmed: 25092301 pmcid: 4143004 doi: 10.1073/pnas.1407435111
Brandt, T., Cavellini, L., Kühlbrandt, W. & Cohen, M. M. A mitofusin-dependent docking ring complex triggers mitochondrial fusion in vitro. eLife 5, e14618 (2016).
pubmed: 27253069 pmcid: 4929004 doi: 10.7554/eLife.14618
Gui, L., Ebner, J. L., Mileant, A., Williams, J. A. & Lee, K. K. Visualization and sequencing of membrane remodeling leading to influenza virus fusion. J. Virol. 90, 6948–6962 (2016).
pubmed: 27226364 pmcid: 4944294 doi: 10.1128/JVI.00240-16
Witkowska, A., Heinz, L. P., Grubmüller, H. & Jahn, R. Tight docking of membranes before fusion represents a metastable state with unique properties. Nat. Commun. 12, 3606 (2021).
pubmed: 34127664 pmcid: 8203622 doi: 10.1038/s41467-021-23722-8
Kasson, P. M., Lindahl, E. & Pande, V. S. Atomic-resolution simulations predict a transition state for vesicle fusion defined by contact of a few lipid tails. PLoS Comput. Biol. 6, e1000829 (2010).
pubmed: 20585620 pmcid: 2891707 doi: 10.1371/journal.pcbi.1000829
Larsson, P. & Kasson, P. M. Lipid tail protrusion in simulations predicts fusogenic activity of influenza fusion peptide mutants and conformational models. PLoS Comput. Biol. 9, e1002950 (2013).
pubmed: 23505359 pmcid: 3591293 doi: 10.1371/journal.pcbi.1002950
Scheidt, H. A. et al. Light-induced lipid mixing implies a causal role of lipid splay in membrane fusion. Biochem. Biophys. Acta Biomembr. 1862, 183483 (2020).
doi: 10.1016/j.bbamem.2020.183438
Yang, L. & Huang, H. W. Observation of a membrane fusion intermediate structure. Science 297, 1877–1879 (2002).
pubmed: 12228719 doi: 10.1126/science.1074354
Aeffner, S., Reusch, T., Weinhausen, B. & Salditt, T. Energetics of stalk intermediates in membrane fusion are controlled by lipid composition. Proc. Natl Acad. Sci. USA 109, E1609–E1618 (2012).
pubmed: 22589300 pmcid: 3382523 doi: 10.1073/pnas.1119442109
Salditt, T. & Aeffner, S. X-ray structural investigations of fusion intermediates: lipid model systems and beyond. Semin. Cell Dev. Biol. 60, 65–77 (2016).
pubmed: 27346739 doi: 10.1016/j.semcdb.2016.06.014
Qian, S. & Rai, D. K. Grazing-angle neutron diffraction study of the water distribution in membrane hemifusion: from the lamellar to rhombohedral phase. J. Phys. Chem. Lett. 9, 5778–5784 (2018).
pubmed: 30111108 doi: 10.1021/acs.jpclett.8b01602
Tiberti, M. L., Antonny, B. & Gautier, R. The transbilayer distribution of polyunsaturated phospholipids determines their facilitating effect on membrane deformation. Soft Matter 16, 1722–1730 (2020).
pubmed: 31916552 doi: 10.1039/C9SM02107H
Chernomordik, L. V. & Kozlov, M. M. Membrane hemifusion: crossing a chasm in two leaps. Cell 123, 375–382 (2005).
pubmed: 16269330 doi: 10.1016/j.cell.2005.10.015
Sharma, S. & Lindau, M. The fusion pore, 60 years after the first cartoon. FEBS Lett. 592, 3542–3562 (2018).
pubmed: 29904915 pmcid: 6231997 doi: 10.1002/1873-3468.13160
Risselada, H. J., Bubnis, G. & Grubmüller, H. Expansion of the fusion stalk and its implication for biological membrane fusion. Proc. Natl Acad. Sci. USA 111, 11043–11048 (2014).
pubmed: 25024174 pmcid: 4121774 doi: 10.1073/pnas.1323221111
Chanturiya, A., Chernomordik, L. V. & Zimmerberg, J. Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers. Proc. Natl Acad. Sci. USA 94, 14423–14428 (1997).
pubmed: 9405628 pmcid: 25008 doi: 10.1073/pnas.94.26.14423
Kienle, N., Kloepper, T. H. & Fasshauer, D. Phylogeny of the SNARE vesicle fusion machinery yields insights into the conservation of the secretory pathway in fungi. BMC Evol. Biol. 9, 19 (2009).
pubmed: 19166604 pmcid: 2639358 doi: 10.1186/1471-2148-9-19
Fasshauer, D., Sutton, R. B., Brunger, A. T. & Jahn, R. Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q- and R-SNAREs. Proc. Natl Acad. Sci. USA 95, 15781–15786 (1998).
pubmed: 9861047 pmcid: 28121 doi: 10.1073/pnas.95.26.15781
Kloepper, T. H., Kienle, C. N. & Fasshauer, D. An elaborate classification of SNARE proteins sheds light on the conservation of the eukaryotic endomembrane system. Mol. Biol. Cell 18, 3463–3471 (2007).
pubmed: 17596510 pmcid: 1951749 doi: 10.1091/mbc.e07-03-0193
Ma, D., Chen, Z. H., He, Z. P. & Huang, X. Q. A SNARE protein identification method based on iLearnPlus to efficiently solve the data imbalance problem. Front. Genet. 12, 818841 (2022).
pubmed: 35154261 pmcid: 8832978 doi: 10.3389/fgene.2021.818841
Kadkova, A., Radecke, J. & Sorensen, J. B. The SNAP-25 protein family. Neuroscience 420, 50–71 (2019).
pubmed: 30267828 doi: 10.1016/j.neuroscience.2018.09.020
McNew, J. A. et al. Ykt6p, a prenylated SNARE essential for endoplasmic reticulum–Golgi transport. J. Biol. Chem. 272, 17776–17783 (1997).
pubmed: 9211930 doi: 10.1074/jbc.272.28.17776
Weimbs, T. et al. A conserved domain is present in different families of vesicular fusion proteins: a new superfamily. Proc. Natl Acad. Sci. USA 94, 3046–3051 (1997).
pubmed: 9096343 pmcid: 20319 doi: 10.1073/pnas.94.7.3046
Ungermann, C. & Wickner, W. Vam7p, a vacuolar SNAP-25 homolog, is required for SNARE complex integrity and vacuole docking and fusion. EMBO J. 17, 3269–3276 (1998).
pubmed: 9628864 pmcid: 1170665 doi: 10.1093/emboj/17.12.3269
Sato, T. K., Darsow, T. & Emr, S. D. Vam7p, a SNAP-25-like molecule, and Vam3p, a syntaxin homolog, function together in yeast vacuolar protein trafficking. Mol. Cell Biol. 18, 5308–5319 (1998).
pubmed: 9710615 pmcid: 109116 doi: 10.1128/MCB.18.9.5308
Itakura, E. & Mizushima, N. Syntaxin 17: the autophagosomal SNARE. Autophagy 9, 917–919 (2013).
pubmed: 23466629 pmcid: 3672300 doi: 10.4161/auto.24109
Masuda, E. S., Huang, B. C., Fisher, J. M., Luo, Y. & Scheller, R. H. Tomosyn binds t-SNARE proteins via a VAMP-like coiled coil. Neuron 21, 479–480 (1998).
pubmed: 9768835 doi: 10.1016/S0896-6273(00)80559-0
Pobbati, A. V., Razeto, A., Boddener, M., Becker, S. & Fasshauer, D. Structural basis for the inhibitory role of tomosyn in exocytosis. J. Biol. Chem. 279, 47192–47200 (2004).
pubmed: 15316007 doi: 10.1074/jbc.M408767200
Scales, S. J., Hesser, B. A., Masuda, E. S. & Scheller, R. H. Amisyn, a novel syntaxin-binding protein that may regulate SNARE complex assembly. J. Biol. Chem. 277, 28271–28279 (2002).
pubmed: 12145319 doi: 10.1074/jbc.M204929200
Hattendorf, D. A., Andreeva, A., Gangar, A., Brennwald, P. J. & Weis, W. I. Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism. Nature 446, 567–571 (2007).
pubmed: 17392788 doi: 10.1038/nature05635
Sinha, R., Ahmed, S., Jahn, R. & Klingauf, J. Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses. Proc. Natl Acad. Sci. USA 108, 14318–14323 (2011).
pubmed: 21844343 pmcid: 3161593 doi: 10.1073/pnas.1101818108
Shi, L. et al. SNARE proteins: one to fuse and three to keep the nascent fusion pore open. Science 335, 1355–1359 (2012).
pubmed: 22422984 pmcid: 3736847 doi: 10.1126/science.1214984
van den Bogaart, G. et al. One SNARE complex is sufficient for membrane fusion. Nat. Struct. Mol. Biol. 17, 358–364 (2010).
pubmed: 20139985 pmcid: 2924150 doi: 10.1038/nsmb.1748
Hanson, P. I., Roth, R., Morisaki, H., Jahn, R. & Heuser, J. E. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 90, 523–535 (1997).
pubmed: 9267032 doi: 10.1016/S0092-8674(00)80512-7
Weber, T. et al. SNAREpins: minimal machinery for membrane fusion. Cell 92, 759–772 (1998).
pubmed: 9529252 doi: 10.1016/S0092-8674(00)81404-X
Walter, A. M., Wiederhold, K., Bruns, D., Fasshauer, D. & Sorensen, J. B. Synaptobrevin N-terminally bound to syntaxin–SNAP-25 defines the primed vesicle state in regulated exocytosis. J. Cell Biol. 188, 401–413 (2010).
pubmed: 20142423 pmcid: 2819690 doi: 10.1083/jcb.200907018
Stein, A., Weber, G., Wahl, M. C. & Jahn, R. Helical extension of the neuronal SNARE complex into the membrane. Nature 460, 525–528 (2009).
pubmed: 19571812 pmcid: 3108252 doi: 10.1038/nature08156
Zhou, P., Bacaj, T., Yang, X., Pang, Z. P. & Sudhof, T. C. Lipid-anchored SNAREs lacking transmembrane regions fully support membrane fusion during neurotransmitter release. Neuron 80, 470–483 (2013).
pubmed: 24120845 doi: 10.1016/j.neuron.2013.09.010
Hong, W. SNAREs and traffic. Biochim. Biophys. Acta 1744, 120–144 (2005).
pubmed: 15893389 doi: 10.1016/j.bbamcr.2005.03.014
Pelham, H. R. SNAREs and the secretory pathway — lessons from yeast. Exp. Cell Res. 247, 1–8 (1999).
pubmed: 10047442 doi: 10.1006/excr.1998.4356
Zwilling, D. et al. Early endosomal SNAREs form a structurally conserved SNARE complex and fuse liposomes with multiple topologies. EMBO J. 26, 9–18 (2007).
pubmed: 17159904 doi: 10.1038/sj.emboj.7601467
Burri, L. & Lithgow, T. A complete set of SNAREs in yeast. Traffic 5, 45–52 (2004).
pubmed: 14675424 doi: 10.1046/j.1600-0854.2003.00151.x
Koike, S. & Jahn, R. SNAREs define targeting specificity of trafficking vesicles by combinatorial interaction with tethering factors. Nat. Commun. 10, 1608 (2019).
pubmed: 30962439 pmcid: 6453939 doi: 10.1038/s41467-019-09617-9
Fasshauer, D., Antonin, W., Subramaniam, V. & Jahn, R. SNARE assembly and disassembly exhibit a pronounced hysteresis. Nat. Struct. Biol. 9, 144–151 (2002).
pubmed: 11786917 doi: 10.1038/nsb750
Zhang, Y. Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers. Protein Sci. 26, 1252–1265 (2017).
pubmed: 28097727 pmcid: 5477538 doi: 10.1002/pro.3116
Wiederhold, K. & Fasshauer, D. Is assembly of the SNARE complex enough to fuel membrane fusion? J. Biol. Chem. 284, 13142–13152 (2009).
doi: 10.1074/jbc.M900703200
Fasshauer, D., Otto, H., Eliason, W. K., Jahn, R. & Brunger, A. T. Structural changes are associated with soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex formation. J. Biol. Chem. 272, 28036–28041 (1997).
pubmed: 9346956 doi: 10.1074/jbc.272.44.28036
Nicholson, K. L. et al. Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Sso1p. Nat. Struct. Biol. 5, 793–802 (1998).
pubmed: 9731774 doi: 10.1038/1834
Ellena, J. F. et al. Dynamic structure of lipid-bound synaptobrevin suggests a nucleation-propagation mechanism for trans-SNARE complex formation. Proc. Natl Acad. Sci. USA 106, 20306–20311 (2009).
pubmed: 19918058 pmcid: 2787132 doi: 10.1073/pnas.0908317106
Liang, B., Kiessling, V. & Tamm, L. K. Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate. Proc. Natl Acad. Sci. USA 110, 19384–19389 (2013).
pubmed: 24218570 pmcid: 3845119 doi: 10.1073/pnas.1314699110
Liang, B., Dawidowski, D., Ellena, J. F., Tamm, L. K. & Cafiso, D. S. The SNARE motif of synaptobrevin exhibits an aqueous-interfacial partitioning that is modulated by membrane curvature. Biochemistry 53, 1485–1494 (2014).
pubmed: 24552121 doi: 10.1021/bi401638u
Lakomek, N. A., Yavuz, H., Jahn, R. & Perez-Lara, A. Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion. Proc. Natl Acad. Sci. USA 116, 8699–8708 (2019).
pubmed: 30975750 pmcid: 6500178 doi: 10.1073/pnas.1813194116
Stief, T. et al. Intrinsic disorder of the neuronal SNARE protein SNAP25a in its pre-fusion conformation. J. Mol. Biol. 435, 168069 (2023).
pubmed: 37003471 doi: 10.1016/j.jmb.2023.168069
Lerman, J. C., Robblee, J., Fairman, R. & Hughson, F. M. Structural analysis of the neuronal SNARE protein syntaxin-1A. Biochemistry 39, 8470–8479 (2000).
pubmed: 10913252 doi: 10.1021/bi0003994
Misura, K. M., Scheller, R. H. & Weis, W. I. Self-association of the H3 region of syntaxin 1A. Implications for intermediates in SNARE complex assembly. J. Biol. Chem. 276, 13273–13282 (2001).
pubmed: 11118447 doi: 10.1074/jbc.M009636200
Sieber, J. J. et al. Anatomy and dynamics of a supramolecular membrane protein cluster. Science 317, 1072–1076 (2007).
pubmed: 17717182 doi: 10.1126/science.1141727
Xiao, W., Poirier, M. A., Bennett, M. K. & Shin, Y. K. The neuronal t-SNARE complex is a parallel four-helix bundle. Nat. Struct. Biol. 8, 308–311 (2001).
pubmed: 11276248 doi: 10.1038/86174
Margittai, M., Fasshauer, D., Pabst, S., Jahn, R. & Langen, R. Homo- and heterooligomeric SNARE complexes studied by site-directed spin labeling. J. Biol. Chem. 276, 13169–13177 (2001).
pubmed: 11278719 doi: 10.1074/jbc.M010653200
Misura, K. M., Gonzalez, L. C. Jr., May, A. P., Scheller, R. H. & Weis, W. I. Crystal structure and biophysical properties of a complex between the N-terminal SNARE region of SNAP25 and syntaxin 1a. J. Biol. Chem. 276, 41301–41309 (2001).
pubmed: 11533035 doi: 10.1074/jbc.M106853200
Hesselbarth, J. & Schmidt, C. Mass spectrometry uncovers intermediates and off-pathway complexes for SNARE complex assembly. Commun. Biol. 6, 198 (2023).
pubmed: 36806321 pmcid: 9941103 doi: 10.1038/s42003-023-04548-0
Dulubova, I. et al. A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J. 18, 4372–4382 (1999).
pubmed: 10449403 pmcid: 1171512 doi: 10.1093/emboj/18.16.4372
Margittai, M. et al. Single-molecule fluorescence resonance energy transfer reveals a dynamic equilibrium between closed and open conformations of syntaxin 1. Proc. Natl Acad. Sci. USA 100, 15516–15521 (2003).
pubmed: 14668446 pmcid: 307599 doi: 10.1073/pnas.2331232100
Fasshauer, D. & Margittai, M. A transient N-terminal interaction of SNAP-25 and syntaxin nucleates SNARE assembly. J. Biol. Chem. 279, 7613–7621 (2004).
pubmed: 14665625 doi: 10.1074/jbc.M312064200
Furukawa, N. & Mima, J. Multiple and distinct strategies of yeast SNAREs to confer the specificity of membrane fusion. Sci. Rep. 4, 4277 (2014).
pubmed: 24589832 pmcid: 3940976 doi: 10.1038/srep04277
Antonin, W. et al. A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function. EMBO J. 19, 6453–6464 (2000).
pubmed: 11101518 pmcid: 305878 doi: 10.1093/emboj/19.23.6453
Wilhelm, B. G. et al. Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344, 1023–1028 (2014).
pubmed: 24876496 doi: 10.1126/science.1252884
Bethani, I. et al. The specificity of SNARE pairing in biological membranes is mediated by both proof-reading and spatial segregation. EMBO J. 26, 3981–3992 (2007).
pubmed: 17717530 pmcid: 1994121 doi: 10.1038/sj.emboj.7601820
Behnia, R. & Munro, S. Organelle identity and the signposts for membrane traffic. Nature 438, 597–604 (2005).
pubmed: 16319879 doi: 10.1038/nature04397
Ungermann, C. & Kummel, D. Structure of membrane tethers and their role in fusion. Traffic 20, 479–490 (2019).
pubmed: 31062920 doi: 10.1111/tra.12655
Archbold, J. K., Whitten, A. E., Hu, S. H., Collins, B. M. & Martin, J. L. SNARE-ing the structures of Sec1/Munc18 proteins. Curr. Opin. Struct. Biol. 29, 44–51 (2014).
pubmed: 25282382 doi: 10.1016/j.sbi.2014.09.003
Toonen, R. F. & Verhage, M. Vesicle trafficking: pleasure and pain from SM genes. Trends Cell Biol. 13, 177–186 (2003).
pubmed: 12667755 doi: 10.1016/S0962-8924(03)00031-X
Yu, I. M. & Hughson, F. M. Tethering factors as organizers of intracellular vesicular traffic. Annu. Rev. Cell Dev. Biol. 26, 137–156 (2010).
pubmed: 19575650 doi: 10.1146/annurev.cellbio.042308.113327
Santana-Molina, C., Gutierrez, F. & Devos, D. P. Homology and modular evolution of CATCHR at the origin of the eukaryotic endomembrane system. Genome Biol. Evol. 13, evab125 (2021).
pubmed: 34061181 pmcid: 8290106 doi: 10.1093/gbe/evab125
Pobbati, A. V., Stein, A. & Fasshauer, D. N- to C-terminal SNARE complex assembly promotes rapid membrane fusion. Science 313, 673–676 (2006).
pubmed: 16888141 doi: 10.1126/science.1129486
Liu, Y. et al. SNARE zippering is suppressed by a conformational constraint that Is removed by v-SNARE splitting. Cell Rep. 34, 108611 (2021).
pubmed: 33440145 pmcid: 7837384 doi: 10.1016/j.celrep.2020.108611
Gerber, S. H. et al. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science 321, 1507–1510 (2008).
pubmed: 18703708 pmcid: 3235364 doi: 10.1126/science.1163174
Andre, T. et al. The interaction of Munc18-1 helix 11 and 12 with the central region of the VAMP2 SNARE motif is essential for SNARE templating and synaptic transmission. eNeuro 7, https://doi.org/10.1523/ENEURO.0278-20.2020 (2020).
Stepien, K. P., Xu, J., Zhang, X., Bai, X. C. & Rizo, J. SNARE assembly enlightened by cryo-EM structures of a synaptobrevin–Munc18-1–syntaxin-1 complex. Sci. Adv. 8, eabo5272 (2022).
pubmed: 35731863 pmcid: 9216511 doi: 10.1126/sciadv.abo5272
Dawidowski, D. & Cafiso, D. S. Munc18-1 and the syntaxin-1 N terminus regulate open-closed states in a t-SNARE complex. Structure 24, 392–400 (2016).
pubmed: 26876096 pmcid: 4775345 doi: 10.1016/j.str.2016.01.005
Jakhanwal, S., Lee, C. T., Urlaub, H. & Jahn, R. An activated Q-SNARE/SM protein complex as a possible intermediate in SNARE assembly. EMBO J. 36, 1788–1802 (2017).
pubmed: 28483813 pmcid: 5470040 doi: 10.15252/embj.201696270
Kraynack, B. A. et al. Dsl1p, Tip20p, and the novel Dsl3(Sec39) protein are required for the stability of the Q/t-SNARE complex at the endoplasmic reticulum in yeast. Mol. Biol. Cell 16, 3963–3977 (2005).
pubmed: 15958492 pmcid: 1196311 doi: 10.1091/mbc.e05-01-0056
Tripathi, A., Ren, Y., Jeffrey, P. D. & Hughson, F. M. Structural characterization of Tip20p and Dsl1p, subunits of the Dsl1p vesicle tethering complex. Nat. Struct. Mol. Biol. 16, 114–123 (2009).
pubmed: 19151722 pmcid: 2635920 doi: 10.1038/nsmb.1548
Magdziarek, M. et al. Re-examining how Munc13-1 facilitates opening of syntaxin-1. Protein Sci. 29, 1440–1458 (2020).
pubmed: 32086964 pmcid: 7255523 doi: 10.1002/pro.3844
Rizo, J., David, G., Fealey, M. E. & Jaczynska, K. On the difficulties of characterizing weak protein interactions that are critical for neurotransmitter release. FEBS Open Bio 12, 1912–1938 (2022).
pubmed: 35986639 pmcid: 9623538 doi: 10.1002/2211-5463.13473
Kummel, D. et al. Complexin cross-links prefusion SNAREs into a zigzag array. Nat. Struct. Mol. Biol. 18, 927–933 (2011).
pubmed: 21785414 pmcid: 3410656 doi: 10.1038/nsmb.2101
Zhou, Q. J. et al. Architecture of the synaptotagmin–SNARE machinery for neuronal exocytosis. Nature 525, 62–67 (2015).
pubmed: 26280336 pmcid: 4607316 doi: 10.1038/nature14975
Zhou, Q. J. et al. The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis. Nature 548, 420–425 (2017).
pubmed: 28813412 pmcid: 5757840 doi: 10.1038/nature23484
Brunger, A. T. & Leitz, J. The core complex of the Ca
pubmed: 36243149 doi: 10.1016/j.jmb.2022.167853
Snyder, D. A., Kelly, M. L. & Woodbury, D. J. SNARE complex regulation by phosphorylation. Cell Biochem. Biophys. 45, 111–123 (2006).
pubmed: 16679567 doi: 10.1385/CBB:45:1:111
Warner, H., Mahajan, S. & van den Bogaart, G. Rerouting trafficking circuits through posttranslational SNARE modifications. J. Cell Sci. 135, jcs.260112 (2022).
doi: 10.1242/jcs.260112
Sabatini, B. L. & Regehr, W. G. Timing of synaptic transmission. Annu. Rev. Physiol. 61, 521–542 (1999).
pubmed: 10099700 doi: 10.1146/annurev.physiol.61.1.521
Imig, C. et al. The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron 84, 416–431 (2014).
pubmed: 25374362 doi: 10.1016/j.neuron.2014.10.009
Pang, Z. P. & Sudhof, T. C. Cell biology of Ca
pubmed: 20561775 pmcid: 2963628 doi: 10.1016/j.ceb.2010.05.001
Wolfes, A. C. & Dean, C. The diversity of synaptotagmin isoforms. Curr. Opin. Neurobiol. 63, 198–209 (2020).
pubmed: 32663762 doi: 10.1016/j.conb.2020.04.006
Park, Y. & Ryu, J. K. Models of synaptotagmin-1 to trigger Ca
pubmed: 30004579 doi: 10.1002/1873-3468.13193
Mohrmann, R., Dhara, M. & Bruns, D. Complexins: small but capable. Cell Mol. Life Sci. 72, 4221–4235 (2015).
pubmed: 26245303 pmcid: 4611016 doi: 10.1007/s00018-015-1998-8
Lottermoser, J. A. & Dittman, J. S. Complexin membrane interactions: implications for synapse evolution and function. J. Mol. Biol. 435, 167774 (2023).
pubmed: 35931110 doi: 10.1016/j.jmb.2022.167774
van den Bogaart, G. et al. Membrane protein sequestering by ionic protein–lipid interactions. Nature 479, 552–555 (2011).
pubmed: 22020284 pmcid: 3409895 doi: 10.1038/nature10545
Bai, J., Tucker, W. C. & Chapman, E. R. 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 (2004).
pubmed: 14718921 doi: 10.1038/nsmb709
Li, L. Y. et al. Phosphatidylinositol phosphates as co-activators of Ca
pubmed: 16595652 doi: 10.1074/jbc.M600888200
Söllner, T., Bennett, M. K., Whiteheart, S. W., Scheller, R. H. & Rothman, J. E. A protein assembly–disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75, 409–418 (1993).
pubmed: 8221884 doi: 10.1016/0092-8674(93)90376-2
Puchades, C., Sandate, C. R. & Lander, G. C. The molecular principles governing the activity and functional diversity of AAA plus proteins. Nat. Rev. Mol. Cell Biol. 21, 43–58 (2020).
pubmed: 31754261 doi: 10.1038/s41580-019-0183-6
Khan, Y. A., White, K. I. & Brunger, A. T. The AAA plus superfamily: a review of the structural and mechanistic principles of these molecular machines. Crit. Rev. Biochem. Mol. 57, 156–187 (2021).
doi: 10.1080/10409238.2021.1979460
Wickner, W. & Schekman, R. Membrane fusion. Nat. Struct. Mol. Biol. 15, 658–664 (2008).
pubmed: 18618939 pmcid: 2488960 doi: 10.1038/nsmb.1451
Clary, D. O., Griff, I. C. & Rothman, J. E. SNAPs, a family of NSF attachment proteins involved in intracellular membrane fusion in animals and yeast. Cell 61, 709–721 (1990).
pubmed: 2111733 doi: 10.1016/0092-8674(90)90482-T
Zhao, M. L. et al. Mechanistic insights into the recycling machine of the SNARE complex. Nature 518, 61 (2015).
pubmed: 25581794 pmcid: 4320033 doi: 10.1038/nature14148
Vivona, S. et al. Disassembly of all SNARE complexes by N-ethylmaleimide-sensitive factor (NSF) is initiated by a conserved 1:1 interaction between α-soluble NSF attachment protein (SNAP) and SNARE complex. J. Biol. Chem. 288, 24984–24991 (2013).
pubmed: 23836889 pmcid: 3750193 doi: 10.1074/jbc.M113.489807
Winter, U., Chen, X. & Fasshauer, D. A conserved membrane attachment site in α-SNAP facilitates N-ethylmaleimide-sensitive factor (NSF)-driven SNARE complex disassembly. J. Biol. Chem. 284, 31817–31826 (2009).
pubmed: 19762473 pmcid: 2797252 doi: 10.1074/jbc.M109.045286
Cipriano, D. J. et al. Processive ATP-driven substrate disassembly by the N-ethylmaleimide-sensitive factor (NSF) molecular machine. J. Biol. Chem. 288, 23436–23445 (2013).
pubmed: 23775070 pmcid: 4520572 doi: 10.1074/jbc.M113.476705
White, K. I., Zhao, M., Choi, U. B., Pfuetzner, R. A. & Brunger, A. T. Structural principles of SNARE complex recognition by the AAA plus protein NSF. eLife 7, e38888 (2018).
pubmed: 30198481 pmcid: 6160233 doi: 10.7554/eLife.38888
Ryu, J. K. et al. Spring-loaded unraveling of a single SNARE complex by NSF in one round of ATP turnover. Science 347, 1485–1489 (2015).
pubmed: 25814585 pmcid: 4441202 doi: 10.1126/science.aaa5267
Yavuz, H. et al. Arrest of trans-SNARE zippering uncovers loosely and tightly docked intermediates in membrane fusion. J. Biol. Chem. 293, 8645–8655 (2018).
pubmed: 29666192 pmcid: 5986196 doi: 10.1074/jbc.RA118.003313
Xu, H., Jun, Y., Thompson, J., Yates, J. & Wickner, W. HOPS prevents the disassembly of trans-SNARE complexes by Sec17p/Sec18p during membrane fusion. EMBO J. 29, 1948–1960 (2010).
pubmed: 20473271 pmcid: 2892374 doi: 10.1038/emboj.2010.97
Prinslow, E. A., Stepien, K. P., Pan, Y. Z., Xu, J. J. & Rizo, J. Multiple factors maintain assembled trans-SNARE complexes in the presence of NSF and αSNAP. eLife 8, e38880 (2019).
pubmed: 30657450 pmcid: 6353594 doi: 10.7554/eLife.38880
Lobingier, B. T., Nickerson, D. P., Lo, S. Y. & Merz, A. J. SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18. eLife 3, e02272 (2014).
pubmed: 24837546 pmcid: 4060006 doi: 10.7554/eLife.02272
Zick, M., Orr, A., Schwartz, M. L., Merz, A. J. & Wickner, W. T. Sec17 can trigger fusion of trans-SNARE paired membranes without Sec18. Proc. Natl Acad. Sci. USA 112, E2290–E2297 (2015).
pubmed: 25902545 pmcid: 4426435 doi: 10.1073/pnas.1506409112
Finkelstein, A. V., Bogatyreva, N. S., Ivankov, D. N. & Garbuzynskiy, S. O. Protein folding problem: enigma, paradox, solution. Biophys. Rev. 14, 1255–1272 (2022).
pubmed: 36659994 pmcid: 9842845 doi: 10.1007/s12551-022-01000-1
Manca, F. et al. SNARE machinery is optimized for ultrafast fusion. Proc. Natl Acad. Sci. USA 116, 2435–2442 (2019).
pubmed: 30700546 pmcid: 6377469 doi: 10.1073/pnas.1820394116
Dubuke, M. L. & Munson, M. The secret life of tethers: the role of tethering factors in SNARE complex regulation. Front. Cell Dev. Biol. 4, 42 (2016).
pubmed: 27243006 pmcid: 4860414 doi: 10.3389/fcell.2016.00042
Baker, R. W. & Hughson, F. M. Chaperoning SNARE assembly and disassembly. Nat. Rev. Mol. Cell Biol. 17, 465–479 (2016).
pubmed: 27301672 pmcid: 5471617 doi: 10.1038/nrm.2016.65
Chamberlain, L. H., Burgoyne, R. D. & Gould, G. W. SNARE proteins are highly enriched in lipid rafts in PC12 cells: implications for the spatial control of exocytosis. Proc. Natl Acad. Sci. USA 98, 5619–5624 (2001).
pubmed: 11331757 pmcid: 33262 doi: 10.1073/pnas.091502398
Lang, T. et al. SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J. 20, 2202–2213 (2001).
pubmed: 11331586 pmcid: 125434 doi: 10.1093/emboj/20.9.2202
Barg, S., Knowles, M. K., Chen, X., Midorikawa, M. & Almers, W. Syntaxin clusters assemble reversibly at sites of secretory granules in live cells. Proc. Natl Acad. Sci. USA 107, 20804–20809 (2010).
pubmed: 21076041 pmcid: 2996446 doi: 10.1073/pnas.1014823107
Li, M. L., Oh, T. J., Fan, H. X., Diao, J. J. & Zhang, K. Syntaxin clustering and optogenetic control for synaptic membrane fusion. J. Mol. Biol. 432, 4773–4782 (2020).
pubmed: 32682743 doi: 10.1016/j.jmb.2020.07.005
Gandasi, N. R. & Barg, S. Contact-induced clustering of syntaxin and munc18 docks secretory granules at the exocytosis site. Nat. Commun. 5, 3914 (2014).
pubmed: 24835618 doi: 10.1038/ncomms4914
Koike, S. & Jahn, R. SNARE proteins: zip codes in vesicle targeting. Biochem. J. 479, 273–288 (2022).
pubmed: 35119456 doi: 10.1042/BCJ20210719
Hernandez, J. M. et al. Membrane fusion intermediates via directional and full assembly of the SNARE complex. Science 336, 1581–1584 (2012).
pubmed: 22653732 pmcid: 3677693 doi: 10.1126/science.1221976
Ginger, L. et al. Arrangements of proteins at reconstituted synaptic vesicle fusion sites depend on membrane separation. FEBS Lett. 594, 3450–3463 (2020).
pubmed: 32860428 pmcid: 7711843 doi: 10.1002/1873-3468.13916
Kiessling, V. et al. A molecular mechanism for calcium-mediated synaptotagmin-triggered exocytosis. Nat. Struct. Mol. Biol. 25, 911 (2018).
pubmed: 30291360 pmcid: 6176490 doi: 10.1038/s41594-018-0130-9
Risselada, H. J. & Mayer, A. SNAREs, tethers and SM proteins: how to overcome the final barriers to membrane fusion? Biochem. J. 477, 243–258 (2020).
pubmed: 31951000 doi: 10.1042/BCJ20190050
Domanska, M. K., Kiessling, V. & Tamm, L. K. Docking and fast fusion of synaptobrevin vesicles depends on the lipid compositions of the vesicle and the acceptor SNARE complex-containing target membrane. Biophys. J. 99, 2936–2946 (2010).
pubmed: 21044591 pmcid: 2965956 doi: 10.1016/j.bpj.2010.09.011
Wang, L., Seeley, E. S., Wickner, W. & Merz, A. J. Vacuole fusion at a ring of vertex docking sites leaves membrane fragments within the organelle. Cell 108, 357–369 (2002).
pubmed: 11853670 doi: 10.1016/S0092-8674(02)00632-3
Rizzoli, S. O. & Betz, W. J. The structural organization of the readily releasable pool of synaptic vesicles. Science 303, 2037–2039 (2004).
pubmed: 15044806 doi: 10.1126/science.1094682
Pieren, M., Desfougeres, Y., Michaillat, L., Schmidt, A. & Mayer, A. Vacuolar SNARE protein transmembrane domains serve as nonspecific membrane anchors with unequal roles in lipid mixing. J. Biol. Chem. 290, 12821–12832 (2015).
pubmed: 25817997 pmcid: 4432298 doi: 10.1074/jbc.M115.647776
Dhara, M. et al. Synergistic actions of v-SNARE transmembrane domains and membrane-curvature modifying lipids in neurotransmitter release. eLife 9, e55152 (2020).
pubmed: 32391794 pmcid: 7239655 doi: 10.7554/eLife.55152
Hu, Y. R., Zhu, L. & Ma, C. Structural roles for the juxtamembrane linker region and transmembrane region of synaptobrevin 2 in membrane fusion. Front. Cell Dev. Biol. 8, 609708 (2021).
pubmed: 33490074 pmcid: 7815645 doi: 10.3389/fcell.2020.609708
Grote, E., Baba, M., Ohsumi, Y. & Novick, P. J. Geranylgeranylated SNAREs are dominant inhibitors of membrane fusion. J. Cell Biol. 151, 453–466 (2000).
pubmed: 11038190 pmcid: 2192637 doi: 10.1083/jcb.151.2.453
Chang, C. W., Chiang, C. W., Gaffaney, J. D., Chapman, E. R. & Jackson, M. B. Lipid-anchored synaptobrevin provides little or no support for exocytosis or liposome fusion. J. Biol. Chem. 291, 2848–2857 (2016).
pubmed: 26663078 doi: 10.1074/jbc.M115.701169
Ucar, H. et al. Mechanical actions of dendritic-spine enlargement on presynaptic exocytosis. Nature 600, 686–689 (2021).
pubmed: 34819666 doi: 10.1038/s41586-021-04125-7
Rosenmund, C. & Stevens, C. F. Definition of the readily releasable pool of vesicles at hippocampal synapses. Neuron 16, 1197–1207 (1996).
pubmed: 8663996 doi: 10.1016/S0896-6273(00)80146-4
Chakraborty, H., Tarafdar, P. K., Bruno, M. J., Sengupta, T. & Lentz, B. R. Activation thermodynamics of poly(ethylene glycol)-mediated model membrane fusion support mechanistic models of stalk and pore formation. Biophys. J. 102, 2751–2760 (2012).
pubmed: 22735525 pmcid: 3379029 doi: 10.1016/j.bpj.2012.04.053
D’Agostino, M., Risselada, H. J., Lurick, A., Ungermann, C. & Mayer, A. A tethering complex drives the terminal stage of SNARE-dependent membrane fusion. Nature 551, 634–638 (2017).
pubmed: 29088698 doi: 10.1038/nature24469
Orr, A., Song, H. & Wickner, W. Fusion with wild-type SNARE domains is controlled by juxtamembrane domains, transmembrane anchors, and Sec17. Mol. Biol. Cell 33, ar38 (2022).
pubmed: 35171720 pmcid: 9282010 doi: 10.1091/mbc.E21-11-0583
Lindau, M. & Almers, W. Structure and function of fusion pores in exocytosis and ectoplasmic membrane fusion. Curr. Opin. Cell Biol. 7, 509–517 (1995).
pubmed: 7495570 doi: 10.1016/0955-0674(95)80007-7
Chang, C. W., Chiang, C. W. & Jackson, M. B. Fusion pores and their control of neurotransmitter and hormone release. J. Gen. Physiol. 149, 301–322 (2017).
pubmed: 28167663 pmcid: 5339513 doi: 10.1085/jgp.201611724
Spruce, A. E., Breckenridge, L. J., Lee, A. K. & Almers, W. Properties of the fusion pore that forms during exocytosis of a mast cell secretory vesicle. Neuron 4, 643–654 (1990).
pubmed: 2344404 doi: 10.1016/0896-6273(90)90192-I
Chow, R. H., von Ruden, L. & Neher, E. Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells. Nature 356, 60–63 (1992).
pubmed: 1538782 doi: 10.1038/356060a0
Takahashi, N., Kishimoto, T., Nemoto, T., Kadowaki, T. & Kasai, H. Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet. Science 297, 1349–1352 (2002).
pubmed: 12193788 doi: 10.1126/science.1073806
Lindau, M. & Alvarez, D. T. The fusion pore. Biochim. Biophys. Acta 1641, 167–173 (2003).
pubmed: 12914957 doi: 10.1016/S0167-4889(03)00085-5
Fesce, R., Grohovaz, F., Valtorta, F. & Meldolesi, J. Neurotransmitter release: fusion or ‘kiss-and-run’? Trends Cell Biol. 4, 1–4 (1994).
pubmed: 14731821 doi: 10.1016/0962-8924(94)90025-6
Alabi, A. A. & Tsien, R. W. Perspectives on kiss-and-run: role in exocytosis, endocytosis, and neurotransmission. Annu. Rev. Physiol. 75, 393–422 (2013).
pubmed: 23245563 doi: 10.1146/annurev-physiol-020911-153305
Watanabe, S. et al. Ultrafast endocytosis at mouse hippocampal synapses. Nature 504, 242–247 (2013).
pubmed: 24305055 pmcid: 3957339 doi: 10.1038/nature12809
Holroyd, P., Lang, T., Wenzel, D., De Camilli, P. & Jahn, R. Imaging direct, dynamin-dependent recapture of fusing secretory granules on plasma membrane lawns from PC12 cells. Proc. Natl Acad. Sci. USA 99, 16806–16811 (2002).
pubmed: 12486251 pmcid: 139225 doi: 10.1073/pnas.222677399
Taraska, J. W., Perrais, D., Ohara-Imaizumi, M., Nagamatsu, S. & Almers, W. Secretory granules are recaptured largely intact after stimulated exocytosis in cultured endocrine cells. Proc. Natl Acad. Sci. USA 100, 2070–2075 (2003).
pubmed: 12538853 pmcid: 149960 doi: 10.1073/pnas.0337526100
Taraska, J. W. & Almers, W. Bilayers merge even when exocytosis is transient. Proc. Natl Acad. Sci. USA 101, 8780–8785 (2004).
pubmed: 15173592 pmcid: 423272 doi: 10.1073/pnas.0401316101
Jackson, M. B. & Chapman, E. R. Fusion pores and fusion machines in Ca
pubmed: 16689631 doi: 10.1146/annurev.biophys.35.040405.101958
Wu, Z., Thiyagarajan, S., O’Shaughnessy, B. & Karatekin, E. Regulation of exocytotic fusion pores by SNARE protein transmembrane domains. Front. Mol. Neurosci. 10, 315 (2017).
pubmed: 29066949 pmcid: 5641348 doi: 10.3389/fnmol.2017.00315
Hastoy, B. et al. A central small amino acid in the VAMP2 transmembrane domain regulates the fusion pore in exocytosis. Sci. Rep. 7, 2835 (2017).
pubmed: 28588281 pmcid: 5460238 doi: 10.1038/s41598-017-03013-3
Dhara, M., Mohrmann, R. & Bruns, D. v-SNARE function in chromaffin cells. Pflug. Arch. 470, 169–180 (2018).
doi: 10.1007/s00424-017-2066-z
Zhang, Y., Ma, L. & Bao, H. Energetics, kinetics, and pathways of SNARE assembly in membrane fusion. Crit. Rev. Biochem. Mol. Biol. 57, 443–460 (2022).
pubmed: 36151854 pmcid: 9588726 doi: 10.1080/10409238.2022.2121804
Bretou, M., Anne, C. & Darchen, F. A fast mode of membrane fusion dependent on tight SNARE zippering. J. Neurosci. 28, 8470–8476 (2008).
pubmed: 18716205 pmcid: 6671043 doi: 10.1523/JNEUROSCI.0860-08.2008
Stratton, B. S. et al. Cholesterol increases the openness of SNARE-mediated flickering fusion pores. Biophys. J. 110, 1538–1550 (2016).
pubmed: 27074679 pmcid: 4833774 doi: 10.1016/j.bpj.2016.02.019
Wu, L., Courtney, K. C. & Chapman, E. R. Cholesterol stabilizes recombinant exocytic fusion pores by altering membrane bending rigidity. Biophys. J. 120, 1367–1377 (2021).
pubmed: 33582136 pmcid: 8105710 doi: 10.1016/j.bpj.2021.02.005
Kreutzberger, A. J., Kiessling, V. & Tamm, L. K. High cholesterol obviates a prolonged hemifusion intermediate in fast SNARE-mediated membrane fusion. Biophys. J. 109, 319–329 (2015).
pubmed: 26200867 pmcid: 4621810 doi: 10.1016/j.bpj.2015.06.022
Kreutzberger, A. J. B. et al. Asymmetric phosphatidylethanolamine distribution controls fusion pore lifetime and probability. Biophys. J. 113, 1912–1915 (2017).
pubmed: 29037600 pmcid: 5685784 doi: 10.1016/j.bpj.2017.09.014
Wu, Z. Y. et al. Nanodisc-cell fusion: control of fusion pore nucleation and lifetimes by SNARE protein transmembrane domains. Sci. Rep. 6, 27287 (2016).
pubmed: 27264104 pmcid: 4893671 doi: 10.1038/srep27287
Bao, H. et al. Exocytotic fusion pores are composed of both lipids and proteins. Nat. Struct. Mol. Biol. 23, 67–73 (2016).
pubmed: 26656855 doi: 10.1038/nsmb.3141
Bao, H. et al. Dynamics and number of trans-SNARE complexes determine nascent fusion pore properties. Nature 554, 260–263 (2018).
pubmed: 29420480 pmcid: 5808578 doi: 10.1038/nature25481
Das, D., Bao, H., Courtney, K. C., Wu, L. & Chapman, E. R. Resolving kinetic intermediates during the regulated assembly and disassembly of fusion pores. Nat. Commun. 11, 231 (2020).
pubmed: 31932584 pmcid: 6957489 doi: 10.1038/s41467-019-14072-7
Karatekin, E. Toward a unified picture of the exocytotic fusion pore. FEBS Lett. 592, 3563–3585 (2018).
pubmed: 30317539 pmcid: 6353554 doi: 10.1002/1873-3468.13270
Sharma, S. & Lindau, M. Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex. Proc. Natl Acad. Sci. USA 115, 12751–12756 (2018).
pubmed: 30482862 pmcid: 6294955 doi: 10.1073/pnas.1816495115
Grushin, K., Kalyana Sundaram, R. V., Sindelar, C. V. & Rothman, J. E. Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release. Proc. Natl Acad. Sci. USA 119, e2121259119 (2022).
pubmed: 35135883 pmcid: 8851502 doi: 10.1073/pnas.2121259119
Holt, M., Riedel, D., Stein, A., Schuette, C. & Jahn, R. Synaptic vesicles are constitutively active fusion machines that function independently of Ca
pubmed: 18485705 pmcid: 2481520 doi: 10.1016/j.cub.2008.04.069
Park, Y. et al. Controlling synaptotagmin activity by electrostatic screening. Nat. Struct. Mol. Biol. 19, 991–997 (2012).
pubmed: 22940675 pmcid: 3465474 doi: 10.1038/nsmb.2375
Kreutzberger, A. J. B. et al. Reconstitution of calcium-mediated exocytosis of dense-core vesicles. Sci. Adv. 3, e1603208 (2017).
pubmed: 28776026 pmcid: 5517108 doi: 10.1126/sciadv.1603208
Kiessling, V. et al. Rapid fusion of synaptic vesicles with reconstituted target SNARE membranes. Biophys. J. 104, 1950–1958 (2013).
pubmed: 23663838 pmcid: 3647153 doi: 10.1016/j.bpj.2013.03.038
Bello, O. D., Auclair, S. M., Rothman, J. E. & Krishnakumar, S. S. Using ApoE nanolipoprotein particles to analyze SNARE-induced fusion pores. Langmuir 32, 3015–3023 (2016).
pubmed: 26972604 pmcid: 4946868 doi: 10.1021/acs.langmuir.6b00245
Malsam, J. et al. Complexin arrests a pool of docked vesicles for fast Ca
pubmed: 22705946 pmcid: 3411073 doi: 10.1038/emboj.2012.164
Schuette, C. G. et al. Determinants of liposome fusion mediated by synaptic SNARE proteins. Proc. Natl Acad. Sci. USA 101, 2858–2863 (2004).
pubmed: 14981239 pmcid: 365710 doi: 10.1073/pnas.0400044101
Nickel, W. et al. Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs. Proc. Natl Acad. Sci. USA 96, 12571–12576 (1999).
pubmed: 10535963 pmcid: 22994 doi: 10.1073/pnas.96.22.12571
Diao, J. et al. Single-vesicle fusion assay reveals Munc18-1 binding to the SNARE core is sufficient for stimulating membrane fusion. ACS Chem. Neurosci. 1, 168–174 (2010).
pubmed: 20300453 pmcid: 2841011 doi: 10.1021/cn900034p
Kyoung, M. et al. In vitro system capable of differentiating fast Ca
pubmed: 21705659 pmcid: 3141984 doi: 10.1073/pnas.1107900108
Yoon, T. Y., Okumus, B., Zhang, F., Shin, Y. K. & Ha, T. Multiple intermediates in SNARE-induced membrane fusion. Proc. Natl Acad. Sci. USA 103, 19731–19736 (2006).
pubmed: 17167056 pmcid: 1698870 doi: 10.1073/pnas.0606032103
Cypionka, A. et al. Discrimination between docking and fusion of liposomes reconstituted with neuronal SNARE-proteins using FCS. Proc. Natl Acad. Sci. USA 106, 18575–18580 (2009).
pubmed: 19843696 pmcid: 2764736 doi: 10.1073/pnas.0906677106
Bhalla, A., Chicka, M. C., Tucker, W. C. & Chapman, E. R. Ca
pubmed: 16565726 doi: 10.1038/nsmb1076
Ma, C., Su, L., Seven, A. B., Xu, Y. & Rizo, J. Reconstitution of the vital functions of Munc18 and Munc13 in neurotransmitter release. Science 339, 421–425 (2013).
pubmed: 23258414 doi: 10.1126/science.1230473
Tareste, D., Shen, J., Melia, T. J. & Rothman, J. E. SNAREpin/Munc18 promotes adhesion and fusion of large vesicles to giant membranes. Proc. Natl Acad. Sci. USA 105, 2380–2385 (2008).
pubmed: 18268324 pmcid: 2268145 doi: 10.1073/pnas.0712125105
Fix, M. et al. Imaging single membrane fusion events mediated by SNARE proteins. Proc. Natl Acad. Sci. USA 101, 7311–7316 (2004).
pubmed: 15123811 pmcid: 409915 doi: 10.1073/pnas.0401779101
Bowen, M. E., Weninger, K., Brunger, A. T. & Chu, S. Single molecule observation of liposome-bilayer fusion thermally induced by soluble N-ethyl maleimide sensitive-factor attachment protein receptors (SNAREs). Biophys. J. 87, 3569–3584 (2004).
pubmed: 15347585 pmcid: 1304822 doi: 10.1529/biophysj.104.048637
Karatekin, E. et al. A fast, single-vesicle fusion assay mimics physiological SNARE requirements. Proc. Natl Acad. Sci. USA 107, 3517–3521 (2010).
pubmed: 20133592 pmcid: 2840481 doi: 10.1073/pnas.0914723107
Domanska, M. K., Kiessling, V., Stein, A., Fasshauer, D. & Tamm, L. K. Single vesicle millisecond fusion kinetics reveals number of SNARE complexes optimal for fast SNARE-mediated membrane fusion. J. Biol. Chem. 284, 32158–32166 (2009).
pubmed: 19759010 pmcid: 2797286 doi: 10.1074/jbc.M109.047381
Kiessling, V., Domanska, M. K. & Tamm, L. K. Single SNARE-mediated vesicle fusion observed in vitro by polarized TIRFM. Biophys. J. 99, 4047–4055 (2010).
pubmed: 21156148 pmcid: 3000493 doi: 10.1016/j.bpj.2010.10.022
Schwenen, L. L. et al. Resolving single membrane fusion events on planar pore-spanning membranes. Sci. Rep. 5, 12006 (2015).
pubmed: 26165860 pmcid: 4499801 doi: 10.1038/srep12006
Sutton, R. B., Fasshauer, D., Jahn, R. & Brunger, A. T. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 395, 347–353 (1998).
pubmed: 9759724 doi: 10.1038/26412
Tucker, W. C., Weber, T. & Chapman, E. R. Reconstitution of Ca
pubmed: 15044754 doi: 10.1126/science.1097196
van den Bogaart, G. et al. Synaptotagmin-1 may be a distance regulator acting upstream of SNARE nucleation. Nat. Struct. Mol. Biol. 18, 805–812 (2011).
pubmed: 21642968 pmcid: 3130798 doi: 10.1038/nsmb.2061
Zdanowicz, R. et al. Complexin binding to membranes and acceptor t-SNAREs explains its clamping effect on fusion. Biophys. J. 113, 1235–1250 (2017).
pubmed: 28456331 pmcid: 5607037 doi: 10.1016/j.bpj.2017.04.002
Li, F. et al. A half-zippered SNARE complex represents a functional intermediate in membrane fusion. J. Am. Chem. Soc. 136, 3456–3464 (2014).
pubmed: 24533674 pmcid: 3985920 doi: 10.1021/ja410690m
Brunger, A. T. et al. The pre-synaptic fusion machinery. Curr. Opin. Struct. Biol. 54, 179–188 (2019).
pubmed: 30986753 pmcid: 6939388 doi: 10.1016/j.sbi.2019.03.007
Li, X. et al. Symmetrical organization of proteins under docked synaptic vesicles. FEBS Lett. 593, 144–153 (2019).
pubmed: 30561792 pmcid: 6353562 doi: 10.1002/1873-3468.13316
Zhu, J. et al. Synaptotagmin rings as high-sensitivity regulators of synaptic vesicle docking and fusion. Proc. Natl Acad. Sci. USA 119, e2208337119 (2022).
pubmed: 36103579 pmcid: 9499556 doi: 10.1073/pnas.2208337119
Gao, Y. et al. Single reconstituted neuronal SNARE complexes zipper in three distinct stages. Science 337, 1340–1343 (2012).
pubmed: 22903523 pmcid: 3677750 doi: 10.1126/science.1224492
Park, Y. et al. Synaptotagmin-1 binds to PIP2-containing membrane but not to SNAREs at physiological ionic strength. Nat. Struct. Mol. Biol. 22, 815–823 (2015).
pubmed: 26389740 pmcid: 4596797 doi: 10.1038/nsmb.3097

Auteurs

Reinhard Jahn (R)

Laboratory of Neurobiology, Max-Planck Institute for Multidisciplinary Sciences, Göttingen, Germany. rjahn@mpinat.mpg.de.

David C Cafiso (DC)

Department of Chemistry, University of Virginia, Charlottesville, VA, USA.

Lukas K Tamm (LK)

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA, USA.

Classifications MeSH