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.


Logo for

Science 328 (5979): 760-763

Copyright © 2010 by the American Association for the Advancement of Science

Dynamic Ca2+-Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1

Han-Ki Lee,1,* Yoosoo Yang,3,* Zengliu Su,4,* Changbong Hyeon,5 Tae-Sun Lee,1 Hong-Won Lee,1 Dae-Hyuk Kweon,3 Yeon-Kyun Shin,4,6,{dagger} Tae-Young Yoon1,2,{dagger}

Abstract: In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca2+ levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca2+-triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca2+ sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca2+ level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca2+ levels and may function as a dynamic presynaptic Ca2+ sensor to control the probability of neurotransmitter release.

1 Department of Physics, KAIST, Daejeon 305-701, South Korea.
2 Institute for the BioCentury, KAIST, Daejeon 305-701, South Korea.
3 Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 4400-746, South Korea.
4 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, 4152 Molecular Biology Building, Ames, IA 50011, USA.
5 School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, South Korea.
6 Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang 790-784, South Korea.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: colishin{at} (Y.-K.S.); tyyoon{at} (T.-Y.Y.)

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.
D. Parisotto, M. Pfau, A. Scheutzow, K. Wild, M. P. Mayer, J. Malsam, I. Sinning, and T. H. Sollner (2014)
J. Biol. Chem. 289, 9639-9650
   Abstract »    Full Text »    PDF »
Structural insights into the Ca2+ and PI(4,5)P2 binding modes of the C2 domains of rabphilin 3A and synaptotagmin 1.
J. Guillen, C. Ferrer-Orta, M. Buxaderas, D. Perez-Sanchez, M. Guerrero-Valero, G. Luengo-Gil, J. Pous, P. Guerra, J. C. Gomez-Fernandez, N. Verdaguer, et al. (2013)
PNAS 110, 20503-20508
   Abstract »    Full Text »    PDF »
Reconstitution of the Vital Functions of Munc18 and Munc13 in Neurotransmitter Release.
C. Ma, L. Su, A. B. Seven, Y. Xu, and J. Rizo (2013)
Science 339, 421-425
   Abstract »    Full Text »    PDF »
Fusion pore formation and expansion induced by Ca2+ and synaptotagmin 1.
Y. Lai, J. Diao, Y. Liu, Y. Ishitsuka, Z. Su, K. Schulten, T. Ha, and Y.-K. Shin (2013)
PNAS 110, 1333-1338
   Abstract »    Full Text »    PDF »
Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis.
H. Kasai, N. Takahashi, and H. Tokumaru (2012)
Physiol Rev 92, 1915-1964
   Abstract »    Full Text »    PDF »
Complexin arrests a pool of docked vesicles for fast Ca2+-dependent release.
J. Malsam, D. Parisotto, T. A. M. Bharat, A. Scheutzow, J. M. Krause, J. A. G. Briggs, and T. H. Sollner (2012)
EMBO J. 31, 3270-3281
   Abstract »    Full Text »    PDF »
Cis- and trans-membrane interactions of synaptotagmin-1.
W. Vennekate, S. Schroder, C.-C. Lin, G. van den Bogaart, M. Grunwald, R. Jahn, and P. J. Walla (2012)
PNAS 109, 11037-11042
   Abstract »    Full Text »    PDF »
Solution single-vesicle assay reveals PIP2-mediated sequential actions of synaptotagmin-1 on SNAREs.
J.-Y. Kim, B.-K. Choi, M.-G. Choi, S.-A. Kim, Y. Lai, Y.-K. Shin, and N. K. Lee (2012)
EMBO J. 31, 2144-2155
   Abstract »    Full Text »    PDF »
Synaptotagmin 1 Is Necessary for the Ca2+ Dependence of Clathrin-Mediated Endocytosis.
L.-H. Yao, Y. Rao, K. Varga, C.-Y. Wang, P. Xiao, M. Lindau, and L.-W. Gong (2012)
J. Neurosci. 32, 3778-3785
   Abstract »    Full Text »    PDF »
Synaptic proteins promote calcium-triggered fast transition from point contact to full fusion.
J. Diao, P. Grob, D. J. Cipriano, M. Kyoung, Y. Zhang, S. Shah, A. Nguyen, M. Padolina, A. Srivastava, M. Vrljic, et al. (2012)
eLife Sci 1, e00109
   Abstract »    Full Text »    PDF »
Reconstituted synaptotagmin I mediates vesicle docking, priming, and fusion.
Z. Wang, H. Liu, Y. Gu, and E. R. Chapman (2011)
J. Cell Biol. 195, 1159-1170
   Abstract »    Full Text »    PDF »
Reluctance to membrane binding enables accessibility of the synaptobrevin SNARE motif for SNARE complex formation.
K. D. Brewer, W. Li, B. E. Horne, and J. Rizo (2011)
PNAS 108, 12723-12728
   Abstract »    Full Text »    PDF »
In vitro system capable of differentiating fast Ca2+-triggered content mixing from lipid exchange for mechanistic studies of neurotransmitter release.
M. Kyoung, A. Srivastava, Y. Zhang, J. Diao, M. Vrljic, P. Grob, E. Nogales, S. Chu, and A. T. Brunger (2011)
PNAS 108, E304-E313
   Abstract »    Full Text »    PDF »
Inside insight to membrane fusion.
G. van den Bogaart and R. Jahn (2011)
PNAS 108, 11729-11730
   Full Text »    PDF »
Calcineurin-mediated Dephosphorylation of Synaptotagmin VI Is Necessary for Acrosomal Exocytosis.
J. Castillo Bennett, C. M. Roggero, F. E. Mancifesta, and L. S. Mayorga (2010)
J. Biol. Chem. 285, 26269-26278
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882