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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}iastate.edu (Y.-K.S.); tyyoon{at}kaist.ac.kr (T.-Y.Y.)

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