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Science 304 (5668): 289-292

Copyright © 2004 by the American Association for the Advancement of Science

Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis

Xue Han, Chih-Tien Wang, Jihong Bai, Edwin R. Chapman, Meyer B. Jackson*

Abstract: The fusion pore of regulated exocytosis is a channel that connects and spans the vesicle and plasma membranes. The molecular composition of this important intermediate structure of exocytosis is unknown. Here, we found that mutations of some residues within the transmembrane segment of syntaxin (Syx), a plasma membrane protein essential for exocytosis, altered neurotransmitter flux through fusion pores and altered pore conductance. The residues that influenced fusion-pore flux lay along one face of an {alpha}-helical model. Thus, the fusion pore is formed at least in part by a circular arrangement of 5 to 8 Syx transmembrane segments in the plasma membrane.

Department of Physiology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.

* To whom correspondence should be addressed. E-mail: mjackson{at}

Titration of Syntaxin1 in Mammalian Synapses Reveals Multiple Roles in Vesicle Docking, Priming, and Release Probability.
M. Arancillo, S.-W. Min, S. Gerber, A. Munster-Wandowski, Y.-J. Wu, M. Herman, T. Trimbuch, J.-C. Rah, G. Ahnert-Hilger, D. Riedel, et al. (2013)
J. Neurosci. 33, 16698-16714
   Abstract »    Full Text »    PDF »
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A. Megighian, M. Zordan, S. Pantano, M. Scorzeto, M. Rigoni, D. Zanini, O. Rossetto, and C. Montecucco (2013)
J. Cell Sci. 126, 3134-3140
   Abstract »    Full Text »    PDF »
Fusion Pores, SNAREs, and Exocytosis.
N. Vardjan, J. Jorgacevski, and R. Zorec (2013)
Neuroscientist 19, 160-174
   Abstract »    Full Text »    PDF »
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V. Degtyar, I. M. Hafez, C. Bray, and R. S. Zucker (2013)
J. Neurosci. 33, 5507-5523
   Abstract »    Full Text »    PDF »
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H. Kasai, N. Takahashi, and H. Tokumaru (2012)
Physiol Rev 92, 1915-1964
   Abstract »    Full Text »    PDF »
Lipid interaction of the C terminus and association of the transmembrane segments facilitate atlastin-mediated homotypic endoplasmic reticulum fusion.
T. Y. Liu, X. Bian, S. Sun, X. Hu, R. W. Klemm, W. A. Prinz, T. A. Rapoport, and J. Hu (2012)
PNAS 109, E2146-E2154
   Abstract »    Full Text »    PDF »
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R. Long, C.-Y. Hui, A. Jagota, and M. Bykhovskaia (2012)
J R Soc Interface 9, 1555-1567
   Abstract »    Full Text »    PDF »
SNARE Proteins: One to Fuse and Three to Keep the Nascent Fusion Pore Open.
L. Shi, Q.-T. Shen, A. Kiel, J. Wang, H.-W. Wang, T. J. Melia, J. E. Rothman, and F. Pincet (2012)
Science 335, 1355-1359
   Abstract »    Full Text »    PDF »
Comparison of Plasma Membrane Proteomic Changes of Arabidopsis Suspension-Cultured Cells (T87 Line) after Cold and ABA Treatment in Association with Freezing Tolerance Development.
B. Li, D. Takahashi, Y. Kawamura, and M. Uemura (2012)
Plant Cell Physiol. 53, 543-554
   Abstract »    Full Text »    PDF »
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B. Strasser, J. Iwaszkiewicz, O. Michielin, and A. Mayer (2011)
EMBO J. 30, 4126-4141
   Abstract »    Full Text »    PDF »
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Y. Schollmeier, J. M. Krause, S. Kreye, J. Malsam, and T. H. Sollner (2011)
J. Biol. Chem. 286, 30582-30590
   Abstract »    Full Text »    PDF »
Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses.
R. Sinha, S. Ahmed, R. Jahn, and J. Klingauf (2011)
PNAS 108, 14318-14323
   Abstract »    Full Text »    PDF »
Counting the SNAREs needed for membrane fusion.
G. van den Bogaart and R. Jahn (2011)
J Mol Cell Biol 3, 204-205
   Abstract »    Full Text »    PDF »
Munc18-1 Tuning of Vesicle Merger and Fusion Pore Properties.
J. Jorgacevski, M. Potokar, S. Grilc, M. Kreft, W. Liu, J. W. Barclay, J. Buckers, R. Medda, S. W. Hell, V. Parpura, et al. (2011)
J. Neurosci. 31, 9055-9066
   Abstract »    Full Text »    PDF »
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Y. Gutierrez-Martin, D. Bustillo, R. Gomez-Villafuertes, J. Sanchez-Nogueiro, C. Torregrosa-Hetland, T. Binz, L. M. Gutierrez, M. T. Miras-Portugal, and A. R. Artalejo (2011)
J. Biol. Chem. 286, 11370-11381
   Abstract »    Full Text »    PDF »
Single secretory granules of live cells recruit syntaxin-1 and synaptosomal associated protein 25 (SNAP-25) in large copy numbers.
M. K. Knowles, S. Barg, L. Wan, M. Midorikawa, X. Chen, and W. Almers (2010)
PNAS 107, 20810-20815
   Abstract »    Full Text »    PDF »
Role of the synaptobrevin C terminus in fusion pore formation.
A. N. Ngatchou, K. Kisler, Q. Fang, A. M. Walter, Y. Zhao, D. Bruns, J. B. Sorensen, and M. Lindau (2010)
PNAS 107, 18463-18468
   Abstract »    Full Text »    PDF »
Fast Vesicle Fusion in Living Cells Requires at Least Three SNARE Complexes.
R. Mohrmann, H. de Wit, M. Verhage, E. Neher, and J. B. Sorensen (2010)
Science 330, 502-505
   Abstract »    Full Text »    PDF »
Arg206 of SNAP-25 is essential for neuroexocytosis at the Drosophila melanogaster neuromuscular junction.
A. Megighian, M. Scorzeto, D. Zanini, S. Pantano, M. Rigoni, C. Benna, O. Rossetto, C. Montecucco, and M. Zordan (2010)
J. Cell Sci. 123, 3276-3283
   Abstract »    Full Text »    PDF »
Transmembrane-domain determinants for SNARE-mediated membrane fusion.
E. Fdez, M. Martinez-Salvador, M. Beard, P. Woodman, and S. Hilfiker (2010)
J. Cell Sci. 123, 2473-2480
   Abstract »    Full Text »    PDF »
Non-conducting function of the Kv2.1 channel enables it to recruit vesicles for release in neuroendocrine and nerve cells.
L. Feinshreiber, D. Singer-Lahat, R. Friedrich, U. Matti, A. Sheinin, O. Yizhar, R. Nachman, D. Chikvashvili, J. Rettig, U. Ashery, et al. (2010)
J. Cell Sci. 123, 1940-1947
   Abstract »    Full Text »    PDF »
Phosphatidylserine Regulation of Ca2+-triggered Exocytosis and Fusion Pores in PC12 Cells.
Z. Zhang, E. Hui, E. R. Chapman, and M. B. Jackson (2009)
Mol. Biol. Cell 20, 5086-5095
   Abstract »    Full Text »    PDF »
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M. K. Domanska, V. Kiessling, A. Stein, D. Fasshauer, and L. K. Tamm (2009)
J. Biol. Chem. 284, 32158-32166
   Abstract »    Full Text »    PDF »
CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.
D. J. James, J. Kowalchyk, N. Daily, M. Petrie, and T. F. J. Martin (2009)
PNAS 106, 17308-17313
   Abstract »    Full Text »    PDF »
Capture and release of partially zipped trans-SNARE complexes on intact organelles.
M. L. Schwartz and A. J. Merz (2009)
J. Cell Biol. 185, 535-549
   Abstract »    Full Text »    PDF »
Single molecule measurements of mechanical interactions within ternary SNARE complexes and dynamics of their disassembly: SNAP25 vs. SNAP23.
V. Montana, W. Liu, U. Mohideen, and V. Parpura (2009)
J. Physiol. 587, 1943-1960
   Abstract »    Full Text »    PDF »
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J. Tong, P. P. Borbat, J. H. Freed, and Y.-K. Shin (2009)
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   Abstract »    Full Text »    PDF »
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H. Cai, K. Reim, F. Varoqueaux, S. Tapechum, K. Hill, J. B. Sorensen, N. Brose, and R. H. Chow (2008)
PNAS 105, 19538-19543
   Abstract »    Full Text »    PDF »
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K. L. Lynch, R. R.L. Gerona, D. M. Kielar, S. Martens, H. T. McMahon, and T. F.J. Martin (2008)
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   Abstract »    Full Text »    PDF »
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Q. Fang, K. Berberian, L.-W. Gong, I. Hafez, J. B. Sorensen, and M. Lindau (2008)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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R. Friedrich, A. J. Groffen, E. Connell, J. R. T. van Weering, O. Gutman, Y. I. Henis, B. Davletov, and U. Ashery (2008)
J. Neurosci. 28, 6794-6806
   Abstract »    Full Text »    PDF »
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Y. Liu, R. Tewari, J. Ning, A. M. Blagborough, S. Garbom, J. Pei, N. V. Grishin, R. E. Steele, R. E. Sinden, W. J. Snell, et al. (2008)
Genes & Dev. 22, 1051-1068
   Abstract »    Full Text »    PDF »
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A. D. Lam, P. Tryoen-Toth, B. Tsai, N. Vitale, and E. L. Stuenkel (2008)
Mol. Biol. Cell 19, 485-497
   Abstract »    Full Text »    PDF »
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Z. Zhang and M. B. Jackson (2008)
J. Gen. Physiol. 131, 117-124
   Abstract »    Full Text »    PDF »
Elementary properties of spontaneous fusion of peptidergic vesicles: fusion pore gating.
N. Vardjan, M. Stenovec, J. Jorgacevski, M. Kreft, and R. Zorec (2007)
J. Physiol. 585, 655-661
   Abstract »    Full Text »    PDF »
Assays of vacuole fusion resolve the stages of docking, lipid mixing, and content mixing.
Y. Jun and W. Wickner (2007)
PNAS 104, 13010-13015
   Abstract »    Full Text »    PDF »
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E. J. Schwartz, T. Blackmer, T. Gerachshenko, and S. Alford (2007)
J. Neurosci. 27, 5857-5868
   Abstract »    Full Text »    PDF »
Stringent 3Q{middle dot}1R Composition of the SNARE 0-Layer Can Be Bypassed for Fusion by Compensatory SNARE Mutation or by Lipid Bilayer Modification.
R. A. Fratti, K. M. Collins, C. M. Hickey, and W. Wickner (2007)
J. Biol. Chem. 282, 14861-14867
   Abstract »    Full Text »    PDF »
Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells.
K. L. Lynch and T. F. J. Martin (2007)
J. Cell Sci. 120, 617-627
   Abstract »    Full Text »    PDF »
Stimulus-Dependent Alterations in Quantal Neurotransmitter Release.
C. P. Grabner and A. P. Fox (2006)
J Neurophysiol 96, 3082-3087
   Abstract »    Full Text »    PDF »
Calcium signaling and exocytosis in adrenal chromaffin cells..
A. G. Garcia, A. M. Garcia-De-Diego, L. Gandia, R. Borges, and J. Garcia-Sancho (2006)
Physiol Rev 86, 1093-1131
   Abstract »    Full Text »    PDF »
Dissecting docking and tethering of secretory vesicles at the target membrane.
R. F. Toonen, O. Kochubey, H. de Wit, A. Gulyas-Kovacs, B. Konijnenburg, J. B. Sorensen, J. Klingauf, and M. Verhage (2006)
EMBO J. 25, 3725-3737
   Abstract »    Full Text »    PDF »
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S. Nolan, A. E. Cowan, D. E. Koppel, H. Jin, and E. Grote (2006)
Mol. Biol. Cell 17, 2439-2450
   Abstract »    Full Text »    PDF »
Double patch clamp reveals that transient fusion (kiss-and-run) is a major mechanism of secretion in calf adrenal chromaffin cells: high calcium shifts the mechanism from kiss-and-run to complete fusion..
A. Elhamdani, F. Azizi, and C. R. Artalejo (2006)
J. Neurosci. 26, 3030-3036
   Abstract »    Full Text »    PDF »
G protein beta{gamma}-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties..
H. Photowala, T. Blackmer, E. Schwartz, H. E. Hamm, and S. Alford (2006)
PNAS 103, 4281-4286
   Abstract »    Full Text »    PDF »
Sequential N- to C-terminal SNARE complex assembly drives priming and fusion of secretory vesicles.
J. B. Sorensen, K. Wiederhold, E. M. Muller, I. Milosevic, G. Nagy, B. L. de Groot, H. Grubmuller, and D. Fasshauer (2006)
EMBO J. 25, 955-966
   Abstract »    Full Text »    PDF »
Cholesterol and synaptic transmitter release at crayfish neuromuscular junctions.
O. Zamir and M. P. Charlton (2006)
J. Physiol. 571, 83-99
   Abstract »    Full Text »    PDF »
Cysteine-Disulfide Cross-linking to Monitor SNARE Complex Assembly during Endoplasmic Reticulum-Golgi Transport.
J. J. Flanagan and C. Barlowe (2006)
J. Biol. Chem. 281, 2281-2288
   Abstract »    Full Text »    PDF »
Structural transitions in the synaptic SNARE complex during Ca2+-triggered exocytosis.
X. Han and M. B. Jackson (2006)
J. Cell Biol. 172, 281-293
   Abstract »    Full Text »    PDF »
Transition from hemifusion to pore opening is rate limiting for vacuole membrane fusion.
C. Reese and A. Mayer (2005)
J. Cell Biol. 171, 981-990
   Abstract »    Full Text »    PDF »
Alternative Splicing of SNAP-25 Regulates Secretion through Nonconservative Substitutions in the SNARE Domain.
G. Nagy, I. Milosevic, D. Fasshauer, E. M. Muller, B. L. de Groot, T. Lang, M. C. Wilson, and J. B. Sorensen (2005)
Mol. Biol. Cell 16, 5675-5685
   Abstract »    Full Text »    PDF »
Cholesterol facilitates the native mechanism of Ca2+-triggered membrane fusion.
M. A. Churchward, T. Rogasevskaia, J. Hofgen, J. Bau, and J. R. Coorssen (2005)
J. Cell Sci. 118, 4833-4848
   Abstract »    Full Text »    PDF »
Transmembrane glycine zippers: Physiological and pathological roles in membrane proteins.
S. Kim, T.-J. Jeon, A. Oberai, D. Yang, J. J. Schmidt, and J. U. Bowie (2005)
PNAS 102, 14278-14283
   Abstract »    Full Text »    PDF »
SCAMP2 Interacts with Arf6 and Phospholipase D1 and Links Their Function to Exocytotic Fusion Pore Formation in PC12 Cells.
L. Liu, H. Liao, A. Castle, J. Zhang, J. Casanova, G. Szabo, and D. Castle (2005)
Mol. Biol. Cell 16, 4463-4472
   Abstract »    Full Text »    PDF »
Synaptotagmin Isoforms Couple Distinct Ranges of Ca2+, Ba2+, and Sr2+ Concentration to SNARE-mediated Membrane Fusion.
A. Bhalla, W. C. Tucker, and E. R. Chapman (2005)
Mol. Biol. Cell 16, 4755-4764
   Abstract »    Full Text »    PDF »
Selective nucleotide-release from dense-core granules in insulin-secreting cells.
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   Abstract »    Full Text »    PDF »
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J. R. L. Constable, M. E. Graham, A. Morgan, and R. D. Burgoyne (2005)
J. Biol. Chem. 280, 31615-31623
   Abstract »    Full Text »    PDF »
Brevity of the Ca2+ Microdomain and Active Zone Geometry Prevent Ca2+-Sensor Saturation for Neurotransmitter Release.
V. Shahrezaei and K. R. Delaney (2005)
J Neurophysiol 94, 1912-1919
   Abstract »    Full Text »    PDF »
Functions of SNAREs in intracellular membrane fusion and lipid bilayer mixing.
C. Ungermann and D. Langosch (2005)
J. Cell Sci. 118, 3819-3828
   Abstract »    Full Text »    PDF »
Membrane Fusion Induced by Neuronal SNAREs Transits through Hemifusion.
X. Lu, F. Zhang, J. A. McNew, and Y.-K. Shin (2005)
J. Biol. Chem. 280, 30538-30541
   Abstract »    Full Text »    PDF »
SNAREs can promote complete fusion and hemifusion as alternative outcomes.
C. G. Giraudo, C. Hu, D. You, A. M. Slovic, E. V. Mosharov, D. Sulzer, T. J. Melia, and J. E. Rothman (2005)
J. Cell Biol. 170, 249-260
   Abstract »    Full Text »    PDF »
Class II fusion protein of alphaviruses drives membrane fusion through the same pathway as class I proteins.
E. Zaitseva, A. Mittal, D. E. Griffin, and L. V. Chernomordik (2005)
J. Cell Biol. 169, 167-177
   Abstract »    Full Text »    PDF »
Two modes of exocytosis at hippocampal synapses revealed by rate of FM1-43 efflux from individual vesicles.
D. A. Richards, J. Bai, and E. R. Chapman (2005)
J. Cell Biol. 168, 929-939
   Abstract »    Full Text »    PDF »
The Plasma Membrane Q-SNARE Syntaxin 2 Enters the Zymogen Granule Membrane during Exocytosis in the Pancreatic Acinar Cell.
J. A. Pickett, P. Thorn, and J. M. Edwardson (2005)
J. Biol. Chem. 280, 1506-1511
   Abstract »    Full Text »    PDF »
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Sci. STKE 2004, re19
   Abstract »    Full Text »    PDF »
Comment on "Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis".
J. A. Szule and J. R. Coorssen (2004)
Science 306, 813b
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Response to Comment on "Transmembrane Segments of Syntaxin Line the Fusion Pore of Ca2+-Triggered Exocytosis".
X. Han and M. B. Jackson (2004)
Science 306, 813c
   Full Text »    PDF »
Regulation of the Fusion Pore Conductance during Exocytosis by Cyclin-dependent Kinase 5.
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   Abstract »    Full Text »    PDF »

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