Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Originally published in Science Express on 3 May 2007
Science 25 May 2007:
Vol. 316. no. 5828, pp. 1205 - 1208
DOI: 10.1126/science.1142614
Prev | Table of Contents | Next

Reports

How Synaptotagmin Promotes Membrane Fusion

Sascha Martens,1 Michael M. Kozlov,2 Harvey T. McMahon1*

Synaptic vesicles loaded with neurotransmitters are exocytosed in a soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE)–dependent manner after presynaptic depolarization induces calcium ion (Ca2+) influx. The Ca2+ sensor required for fast fusion is synaptotagmin-1. The activation energy of bilayer-bilayer fusion is very high ({approx}40 kBT). We found that, in response to Ca2+ binding, synaptotagmin-1 could promote SNARE-mediated fusion by lowering this activation barrier by inducing high positive curvature in target membranes on C2-domain membrane insertion. Thus, synaptotagmin-1 triggers the fusion of docked vesicles by local Ca2+-dependent buckling of the plasma membrane together with the zippering of SNAREs. This mechanism may be widely used in membrane fusion.

1 Medical Research Council–Laboratory of Molecular Biology, Hills Road, CB2 0QH Cambridge, UK.
2 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.

* To whom correspondence should be addressed. E-mail: hmm{at}mrc-lmb.cam.ac.uk

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Yeast Sec1p Functions before and after Vesicle Docking.
K. Hashizume, Y.-S. Cheng, J. L. Hutton, C.-h. Chiu, and C. M. Carr (2009)
Mol. Biol. Cell 20, 4673-4685
   Abstract »    Full Text »    PDF »
Transmembrane Protein-free Membranes Fuse into Xenopus Nuclear Envelope and Promote Assembly of Functional Pores.
E. R. Rafikova, K. Melikov, C. Ramos, L. Dye, and L. V. Chernomordik (2009)
J. Biol. Chem. 284, 29847-29859
   Abstract »    Full Text »    PDF »
Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release.
O.-H. Shin, J. Xu, J. Rizo, and T. C. Sudhof (2009)
PNAS 106, 16469-16474
   Abstract »    Full Text »    PDF »
Is Assembly of the SNARE Complex Enough to Fuel Membrane Fusion?.
K. Wiederhold and D. Fasshauer (2009)
J. Biol. Chem. 284, 13143-13152
   Abstract »    Full Text »    PDF »
Curvature Dynamics of {alpha}-Synuclein Familial Parkinson Disease Mutants: MOLECULAR SIMULATIONS OF THE MICELLE- AND BILAYER-BOUND FORMS.
J. D. Perlmutter, A. R. Braun, and J. N. Sachs (2009)
J. Biol. Chem. 284, 7177-7189
   Abstract »    Full Text »    PDF »
Synaptotagmin-1 Utilizes Membrane Bending and SNARE Binding to Drive Fusion Pore Expansion.
K. L. Lynch, R. R.L. Gerona, D. M. Kielar, S. Martens, H. T. McMahon, and T. F.J. Martin (2008)
Mol. Biol. Cell 19, 5093-5103
   Abstract »    Full Text »    PDF »
Synaptotagmin C2B Domain Regulates Ca2+-triggered Fusion in Vitro: CRITICAL RESIDUES REVEALED BY SCANNING ALANINE MUTAGENESIS.
J. D. Gaffaney, F. M. Dunning, Z. Wang, E. Hui, and E. R. Chapman (2008)
J. Biol. Chem. 283, 31763-31775
   Abstract »    Full Text »    PDF »
A Fast Mode of Membrane Fusion Dependent on Tight SNARE Zippering.
M. Bretou, C. Anne, and F. Darchen (2008)
J. Neurosci. 28, 8470-8476
   Abstract »    Full Text »    PDF »
Membrane curvature induced by Arf1-GTP is essential for vesicle formation.
R. Beck, Z. Sun, F. Adolf, C. Rutz, J. Bassler, K. Wild, I. Sinning, E. Hurt, B. Brugger, J. Bethune, et al. (2008)
PNAS 105, 11731-11736
   Abstract »    Full Text »    PDF »
Analysis of the Synaptotagmin Family during Reconstituted Membrane Fusion: UNCOVERING A CLASS OF INHIBITORY ISOFORMS.
A. Bhalla, M. C. Chicka, and E. R. Chapman (2008)
J. Biol. Chem. 283, 21799-21807
   Abstract »    Full Text »    PDF »
Ca2+-Dependent, Phospholipid-Binding Residues of Synaptotagmin Are Critical for Excitation-Secretion Coupling In Vivo.
B. E. Paddock, A. R. Striegel, E. Hui, E. R. Chapman, and N. E. Reist (2008)
J. Neurosci. 28, 7458-7466
   Abstract »    Full Text »    PDF »
DOC2B Acts as a Calcium Switch and Enhances Vesicle Fusion.
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 »
Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides.
M.-T. Lee, W.-C. Hung, F.-Y. Chen, and H. W. Huang (2008)
PNAS 105, 5087-5092
   Abstract »    Full Text »    PDF »
Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules.
J. Hu, Y. Shibata, C. Voss, T. Shemesh, Z. Li, M. Coughlin, M. M. Kozlov, T. A. Rapoport, and W. A. Prinz (2008)
Science 319, 1247-1250
   Abstract »    Full Text »    PDF »
PIKfyve Negatively Regulates Exocytosis in Neurosecretory Cells.
S. L. Osborne, P. J. Wen, C. Boucheron, H. N. Nguyen, M. Hayakawa, H. Kaizawa, P. J. Parker, N. Vitale, and F. A. Meunier (2008)
J. Biol. Chem. 283, 2804-2813
   Abstract »    Full Text »    PDF »
Highlights From The Literature.
(2007)
Physiology 22, 299-302
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)