Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly

Wang, Shen; Li, Yun; Gong, Jihong; Ye, Sheng; Yang, Xiaofei; Zhang, Rongguang; Ma, Cong

doi:10.1038/s41467-018-08028-6

Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly

Journal Article · Tue Jan 08 00:00:00 EST 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-018-08028-6· OSTI ID:1510246

^[1]; Li, Yun ^[1]; Gong, Jihong ^[1]; Ye, Sheng ^[2]; Yang, Xiaofei ^[3]; Zhang, Rongguang ^[4]; Ma, Cong ^[1]

Huazhong Univ. of Science and Technology, Wuhan (China)
Chinese Academy of Sciences (CAS), Beijing (China)
South-Central Univ. for Nationalities, Wuhan (China)
Chinese Academy of Sciences (CAS), Beijing (China); Chinese Academy of Sciences, Shanghai (China)

The transition of the Munc18-1/syntaxin-1 complex to the SNARE complex, a key step involved in exocytosis, is regulated by Munc13-1, SNAP-25 and synaptobrevin-2, but the underlying mechanism remains elusive. Here, we identify an interaction between Munc13-1 and the membrane-proximal linker region of synaptobrevin-2, and reveal its essential role in transition and exocytosis. Upon this interaction, Munc13-1 not only recruits synaptobrevin-2-embedded vesicles to the target membrane but also renders the synaptobrevin-2 SNARE motif more accessible to the Munc18-1/syntaxin-1 complex. Afterward, the entry of SNAP-25 leads to a half-zippered SNARE assembly, which eventually dissociates the Munc18-1/syntaxin-1 complex to complete SNARE complex formation. Furthermore, our data suggest that Munc18-1 and Munc13-1 together serve as a functional template to orchestrate SNARE complex assembly.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Key Basic Research Program of China; National Natural Science Foundation of China

OSTI ID:: 1510246

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 10; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (68)

Tomosyn guides SNARE complex formation in coordination with Munc18 and Munc13 Li, Yun; Wang, Shen; Li, Tianzhi FEBS Letters, Vol. 592, Issue 7 https://doi.org/10.1002/1873-3468.13018	journal	February 2018
The Molecular Machinery of Neurotransmitter Release (Nobel Lecture) Südhof, Thomas C. Angewandte Chemie International Edition, Vol. 53, Issue 47 https://doi.org/10.1002/anie.201406359	journal	October 2014
Phosphatidylserine-Dependent Catalysis of Stalk and Pore Formation by Synaptobrevin JMR-TMD Peptide Tarafdar, Pradip K.; Chakraborty, Hirak; Bruno, Michael J. Biophysical Journal, Vol. 109, Issue 9 https://doi.org/10.1016/j.bpj.2015.08.051	journal	November 2015
A Structure-Based Mechanism for Vesicle Capture by the Multisubunit Tethering Complex Dsl1 Ren, Yi; Yip, Calvin K.; Tripathi, Arati Cell, Vol. 139, Issue 6 https://doi.org/10.1016/j.cell.2009.11.002	journal	December 2009
Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle Südhof, Thomas C. Neuron, Vol. 80, Issue 3 https://doi.org/10.1016/j.neuron.2013.10.022	journal	October 2013
Molecular Mechanisms of Synaptic Vesicle Priming by Munc13 and Munc18 Lai, Ying; Choi, Ucheor B.; Leitz, Jeremy Neuron, Vol. 95, Issue 3 https://doi.org/10.1016/j.neuron.2017.07.004	journal	August 2017
Munc18-1 in secretion: lonely Munc joins SNARE team and takes control Toonen, Ruud F. G.; Verhage, Matthijs Trends in Neurosciences, Vol. 30, Issue 11 https://doi.org/10.1016/j.tins.2007.08.008	journal	November 2007
Munc13-1 Is a Presynaptic Phorbol Ester Receptor that Enhances Neurotransmitter Release Betz, Andrea; Ashery, Uri; Rickmann, Michael Neuron, Vol. 21, Issue 1 https://doi.org/10.1016/s0896-6273(00)80520-6	journal	July 1998
Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution Sutton, R. Bryan; Fasshauer, Dirk; Jahn, Reinhard Nature, Vol. 395, Issue 6700 https://doi.org/10.1038/26412	journal	September 1998
Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex Misura, Kira M. S.; Scheller, Richard H.; Weis, William I. Nature, Vol. 404, Issue 6776 https://doi.org/10.1038/35006120	journal	March 2000
Munc18a controls SNARE assembly through its interaction with the syntaxin N-peptide Burkhardt, Pawel; Hattendorf, Douglas A.; Weis, William I. The EMBO Journal, Vol. 27, Issue 7 https://doi.org/10.1038/emboj.2008.37	journal	March 2008
Fast, scalable generation of high‐quality protein multiple sequence alignments using Clustal Omega Sievers, Fabian; Wilm, Andreas; Dineen, David Molecular Systems Biology, Vol. 7, Issue 1 https://doi.org/10.1038/msb.2011.75	journal	January 2011
Molecular machines governing exocytosis of synaptic vesicles Jahn, Reinhard; Fasshauer, Dirk Nature, Vol. 490, Issue 7419 https://doi.org/10.1038/nature11320	journal	October 2012
The primed SNARE–complexin–synaptotagmin complex for neuronal exocytosis Zhou, Qiangjun; Zhou, Peng; Wang, Austin L. Nature, Vol. 548, Issue 7668 https://doi.org/10.1038/nature23484	journal	August 2017
Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles He, Enqi; Wierda, Keimpe; van Westen, Rhode Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15915	journal	June 2017
A single vesicle-vesicle fusion assay for in vitro studies of SNAREs and accessory proteins Diao, Jiajie; Ishitsuka, Yuji; Lee, Hanki Nature Protocols, Vol. 7, Issue 5 https://doi.org/10.1038/nprot.2012.020	journal	April 2012
SNAREs — engines for membrane fusion Jahn, Reinhard; Scheller, Richard H. Nature Reviews Molecular Cell Biology, Vol. 7, Issue 9 https://doi.org/10.1038/nrm2002	journal	August 2006
Munc13 mediates the transition from the closed syntaxin–Munc18 complex to the SNARE complex Ma, Cong; Li, Wei; Xu, Yibin Nature Structural & Molecular Biology, Vol. 18, Issue 5 https://doi.org/10.1038/nsmb.2047	journal	April 2011
Complexin cross-links prefusion SNAREs into a zigzag array Kümmel, Daniel; Krishnakumar, Shyam S.; Radoff, Daniel T. Nature Structural & Molecular Biology, Vol. 18, Issue 8 https://doi.org/10.1038/nsmb.2101	journal	July 2011
Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming Yang, Xiaoyu; Wang, Shen; Sheng, Yi Nature Structural & Molecular Biology, Vol. 22, Issue 7 https://doi.org/10.1038/nsmb.3038	journal	June 2015
Sequential N- to C-terminal SNARE complex assembly drives priming and fusion of secretory vesicles Sørensen, Jakob B.; Wiederhold, Katrin; Müller, Emil M. The EMBO Journal, Vol. 25, Issue 5 https://doi.org/10.1038/sj.emboj.7601003	journal	February 2006
An optimized method for high-titer lentivirus preparations without ultracentrifugation Jiang, Wei; Hua, Rui; Wei, Mengping Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep13875	journal	September 2015
Possible roles for Munc18-1 domain 3a and Syntaxin1 N-peptide and C-terminal anchor in SNARE complex formation Hu, S. -H.; Christie, M. P.; Saez, N. J. Proceedings of the National Academy of Sciences, Vol. 108, Issue 3 https://doi.org/10.1073/pnas.0914906108	journal	December 2010
Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation Colbert, K. N.; Hattendorf, D. A.; Weiss, T. M. Proceedings of the National Academy of Sciences, Vol. 110, Issue 31 https://doi.org/10.1073/pnas.1303753110	journal	July 2013
n-Sec1: a neural-specific syntaxin-binding protein. Pevsner, J.; Hsu, S. C.; Scheller, R. H. Proceedings of the National Academy of Sciences, Vol. 91, Issue 4 https://doi.org/10.1073/pnas.91.4.1445	journal	February 1994
An Extended Helical Conformation in Domain 3a of Munc18-1 Provides a Template for SNARE (Soluble N -Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Complex Assembly Parisotto, Daniel; Pfau, Maximilian; Scheutzow, Andrea Journal of Biological Chemistry, Vol. 289, Issue 14 https://doi.org/10.1074/jbc.m113.514273	journal	February 2014
A Pivotal Role for Pro-335 in Balancing the Dual Functions of Munc18-1 Domain-3a in Regulated Exocytosis Han, Gayoung Anna; Park, Seungmee; Bin, Na-Ryum Journal of Biological Chemistry, Vol. 289, Issue 48 https://doi.org/10.1074/jbc.m114.584805	journal	October 2014
Vps51p Links the VFT Complex to the SNARE Tlg1p Siniossoglou, Symeon; Pelham, Hugh R. B. Journal of Biological Chemistry, Vol. 277, Issue 50 https://doi.org/10.1074/jbc.m209428200	journal	October 2002
A Transient N-terminal Interaction of SNAP-25 and Syntaxin Nucleates SNARE Assembly Fasshauer, Dirk; Margittai, Martin Journal of Biological Chemistry, Vol. 279, Issue 9 https://doi.org/10.1074/jbc.m312064200	journal	December 2003
The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming Kasula, Ravikiran; Chai, Ye Jin; Bademosi, Adekunle T. The Journal of Cell Biology, Vol. 214, Issue 7 https://doi.org/10.1083/jcb.201508118	journal	September 2016
An Elaborate Classification of SNARE Proteins Sheds Light on the Conservation of the Eukaryotic Endomembrane System Kloepper, Tobias H.; Kienle, C. Nickias; Fasshauer, Dirk Molecular Biology of the Cell, Vol. 18, Issue 9 https://doi.org/10.1091/mbc.e07-03-0193	journal	September 2007
Phosphatidylinositol 4,5-Bisphosphate Mediates the Targeting of the Exocyst to the Plasma Membrane for Exocytosis in Mammalian Cells Liu, Jianglan; Zuo, Xiaofeng; Yue, Peng Molecular Biology of the Cell, Vol. 18, Issue 11 https://doi.org/10.1091/mbc.e07-05-0461	journal	November 2007
Evidence that Electrostatic Interactions between Vesicle-associated Membrane Protein 2 and Acidic Phospholipids May Modulate the Fusion of Transport Vesicles with the Plasma Membrane Williams, Dumaine; Vicôgne, Jérome; Zaitseva, Irina Molecular Biology of the Cell, Vol. 20, Issue 23 https://doi.org/10.1091/mbc.e09-04-0284	journal	December 2009
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/s0021889807021206	journal	July 2007
Chaperones That SNARE Neurotransmitter Release Hughson, F. M. Science, Vol. 339, Issue 6118 https://doi.org/10.1126/science.1233801	journal	January 2013
Domain 3a of Munc18-1 plays a crucial role at the priming stage of exocytosis Han, G. A.; Bin, N. -R.; Kang, S. -Y. A. Journal of Cell Science, Vol. 126, Issue 11 https://doi.org/10.1242/jcs.126862	journal	March 2013
Crystal Structures of the Sec1/Munc18 (SM) Protein Vps33, Alone and Bound to the Homotypic Fusion and Vacuolar Protein Sorting (HOPS) Subunit Vps16* Baker, Richard W.; Jeffrey, Philip D.; Hughson, Frederick M. PLoS ONE, Vol. 8, Issue 6 https://doi.org/10.1371/journal.pone.0067409	journal	June 2013
Extension of Helix 12 in Munc18-1 Induces Vesicle Priming Munch, A. S.; Kedar, G. H.; van Weering, J. R. T. Journal of Neuroscience, Vol. 36, Issue 26 https://doi.org/10.1523/jneurosci.0007-16.2016	journal	June 2016
Conformational change of syntaxin linker region induced by Munc13s initiates SNARE complex formation in synaptic exocytosis Wang, Shen; Choi, Ucheor B.; Gong, Jihong The EMBO Journal, Vol. 36, Issue 6 https://doi.org/10.15252/embj.201695775	journal	January 2017
A Stimulation Function of Synaptotagmin-1 in Ternary SNARE Complex Formation Dependent on Munc18 and Munc13 Li, Yun; Wang, Shen; Li, Tianzhi Frontiers in Molecular Neuroscience, Vol. 10 https://doi.org/10.3389/fnmol.2017.00256	journal	August 2017
SNAREpins: Minimal Machinery for Membrane Fusion Weber, Thomas; Zemelman, Boris V.; McNew, James A. Cell, Vol. 92, Issue 6 https://doi.org/10.1016/S0092-8674(00)81404-X	journal	March 1998
Definition of the Readily Releasable Pool of Vesicles at Hippocampal Synapses Rosenmund, Christian; Stevens, Charles F. Neuron, Vol. 16, Issue 6 https://doi.org/10.1016/S0896-6273(00)80146-4	journal	June 1996
Munc13-1 Is a Presynaptic Phorbol Ester Receptor that Enhances Neurotransmitter Release Betz, Andrea; Ashery, Uri; Rickmann, Michael Neuron, Vol. 21, Issue 1 https://doi.org/10.1016/S0896-6273(00)80520-6	journal	July 1998
Complexin-1 Enhances the On-Rate of Vesicle Docking via Simultaneous SNARE and Membrane Interactions Diao, Jiajie; Cipriano, Daniel J.; Zhao, Minglei Journal of the American Chemical Society, Vol. 135, Issue 41 https://doi.org/10.1021/ja407392n	journal	October 2013
Helical extension of the neuronal SNARE complex into the membrane Stein, Alexander; Weber, Gert; Wahl, Markus C. Nature, Vol. 460, Issue 7254 https://doi.org/10.1038/nature08156	journal	July 2009
Sec3 promotes the initial binary t-SNARE complex assembly and membrane fusion Yue, Peng; Zhang, Yubo; Mei, Kunrong Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms14236	journal	January 2017
Synaptic vesicle fusion Rizo, Josep; Rosenmund, Christian Nature Structural & Molecular Biology, Vol. 15, Issue 7 https://doi.org/10.1038/nsmb.1450	journal	July 2008
PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome Sharma, Deepti; De Falco, Louis; Padavattan, Sivaraman Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-13641-0	journal	December 2019
trans-SNARE complex assembly and yeast vacuole membrane fusion Collins, K. M.; Wickner, W. T. Proceedings of the National Academy of Sciences, Vol. 104, Issue 21 https://doi.org/10.1073/pnas.0702290104	journal	May 2007
An Extended Helical Conformation in Domain 3a of Munc18-1 Provides a Template for SNARE (Soluble N -Ethylmaleimide-sensitive Factor Attachment Protein Receptor) Complex Assembly Parisotto, Daniel; Pfau, Maximilian; Scheutzow, Andrea Journal of Biological Chemistry, Vol. 289, Issue 14 https://doi.org/10.1074/jbc.M113.514273	journal	February 2014
A Pivotal Role for Pro-335 in Balancing the Dual Functions of Munc18-1 Domain-3a in Regulated Exocytosis Han, Gayoung Anna; Park, Seungmee; Bin, Na-Ryum Journal of Biological Chemistry, Vol. 289, Issue 48 https://doi.org/10.1074/jbc.M114.584805	journal	October 2014
Vps51p Links the VFT Complex to the SNARE Tlg1p Siniossoglou, Symeon; Pelham, Hugh R. B. Journal of Biological Chemistry, Vol. 277, Issue 50 https://doi.org/10.1074/jbc.M209428200	journal	October 2002
A Transient N-terminal Interaction of SNAP-25 and Syntaxin Nucleates SNARE Assembly Fasshauer, Dirk; Margittai, Martin Journal of Biological Chemistry, Vol. 279, Issue 9 https://doi.org/10.1074/jbc.M312064200	journal	December 2003
Interaction of the conserved oligomeric Golgi complex with t-SNARE Syntaxin5a/Sed5 enhances intra-Golgi SNARE complex stability Shestakova, Anna; Suvorova, Elena; Pavliv, Oleksandra The Journal of Cell Biology, Vol. 179, Issue 6 https://doi.org/10.1083/jcb.200705145	journal	December 2007
HOPS Proofreads the trans -SNARE Complex for Yeast Vacuole Fusion Starai, Vincent J.; Hickey, Christopher M.; Wickner, William Molecular Biology of the Cell, Vol. 19, Issue 6 https://doi.org/10.1091/mbc.e08-01-0077	journal	June 2008
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
N- to C-Terminal SNARE Complex Assembly Promotes Rapid Membrane Fusion Pobbati, A. V. Science, Vol. 313, Issue 5787 https://doi.org/10.1126/science.1129486	journal	August 2006
Reconstitution of the Vital Functions of Munc18 and Munc13 in Neurotransmitter Release Ma, C.; Su, L.; Seven, A. B. Science, Vol. 339, Issue 6118 https://doi.org/10.1126/science.1230473	journal	December 2012
A direct role for the Sec1/Munc18-family protein Vps33 as a template for SNARE assembly Baker, R. W.; Jeffrey, P. D.; Zick, M. Science, Vol. 349, Issue 6252 https://doi.org/10.1126/science.aac7906	journal	September 2015
The Synaptic Vesicle Release Machinery Rizo, Josep; Xu, Junjie Annual Review of Biophysics, Vol. 44, Issue 1 https://doi.org/10.1146/annurev-biophys-060414-034057	journal	June 2015
Extension of Helix 12 in Munc18-1 Induces Vesicle Priming Munch, A. S.; Kedar, G. H.; van Weering, J. R. T. Journal of Neuroscience, Vol. 36, Issue 26 https://doi.org/10.1523/JNEUROSCI.0007-16.2016	journal	June 2016
Membrane-Proximal Tryptophans of Synaptobrevin II Stabilize Priming of Secretory Vesicles Borisovska, M.; Schwarz, Y. N.; Dhara, M. Journal of Neuroscience, Vol. 32, Issue 45 https://doi.org/10.1523/JNEUROSCI.6282-11.2012	journal	November 2012
Phosphatidylserine-Dependent Catalysis of Stalk and Pore Formation by Synaptobrevin JMR-TMD Peptide K., Tarafdar, Pradip; Hirak, Chakraborty,; R., Lentz, Barry The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/7agx-ta02	text	January 2015
The Secret Life of Tethers: The Role of Tethering Factors in SNARE Complex Regulation Dubuke, Michelle L.; Munson, Mary Frontiers in Cell and Developmental Biology, Vol. 4 https://doi.org/10.3389/fcell.2016.00042	journal	May 2016
Synaptotagmin-1 C2B domain interacts simultaneously with SNAREs and membranes to promote membrane fusion Wang, Shen; Li, Yun; Ma, Cong eLife, Vol. 5 https://doi.org/10.7554/eLife.14211	journal	April 2016
Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN Xu, Junjie; Camacho, Marcial; Xu, Yibin eLife, Vol. 6 https://doi.org/10.7554/eLife.22567	journal	February 2017
Autoinhibition of Munc18-1 modulates synaptobrevin binding and helps to enable Munc13-dependent regulation of membrane fusion Sitarska, Ewa; Xu, Junjie; Park, Seungmee eLife, Vol. 6 https://doi.org/10.7554/eLife.24278	journal	May 2017

Cited By (7)

In vitro fusion of single synaptic and dense core vesicles reproduces key physiological properties Kreutzberger, Alex J. B.; Kiessling, Volker; Stroupe, Christopher Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-11873-8	journal	August 2019
Additional file 3 of Identification of residues critical for the extension of Munc18-1 domain 3a Wang, Xianping; Gong, Jihong; Zhu, Le figshare https://doi.org/10.6084/m9.figshare.23682330.v1	dataset	January 2023
Membrane bridging by Munc13-1 is crucial for neurotransmitter release Quade, Bradley; Camacho, Marcial; Zhao, Xiaowei eLife, Vol. 8 https://doi.org/10.7554/elife.42806	journal	February 2019
Maintaining order: COG complex controls Golgi trafficking, processing, and sorting Blackburn, Jessica B.; D'Souza, Zinia; Lupashin, Vladimir V. FEBS Letters, Vol. 593, Issue 17 https://doi.org/10.1002/1873-3468.13570	journal	August 2019
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion Lakomek, Nils-Alexander; Yavuz, Halenur; Jahn, Reinhard Proceedings of the National Academy of Sciences, Vol. 116, Issue 18 https://doi.org/10.1073/pnas.1813194116	journal	April 2019
Munc13-1 MUN domain and Munc18-1 cooperatively chaperone SNARE assembly through a tetrameric complex Shu, Tong; Jin, Huaizhou; Rothman, James E. Proceedings of the National Academy of Sciences, Vol. 117, Issue 2 https://doi.org/10.1073/pnas.1914361117	journal	December 2019
Structural dynamics and transient lipid binding of synaptobrevin-2 tune SNARE assembly and membrane fusion Lakomek, Nils-Alexander; Yavuz, Halenur; Jahn, Reinhard ETH Zurich https://doi.org/10.3929/ethz-b-000342501	text	January 2019

Similar Records

Syntaxin opening by the MUN domain underlies the function of Munc13 in synaptic-vesicle priming

Journal Article · Sun May 31 20:00:00 EDT 2015 · Nature Structural & Molecular Biology · OSTI ID:1259896

Interaction of Munc18 and Syntaxin in the regulation of insulin secretion

Journal Article · Fri Aug 31 00:00:00 EDT 2007 · Biochemical and Biophysical Research Communications · OSTI ID:20991511

Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

Journal Article · Fri Apr 29 00:00:00 EDT 2016 · Biochemical and Biophysical Research Communications · OSTI ID:22596358

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
SNARE
Synaptic vesicle exocytosis
X-ray crystallography

Munc18 and Munc13 serve as a functional template to orchestrate neuronal SNARE complex assembly

Citation Formats

References (68)

Cited By (7)

Similar Records

Related Subjects