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

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 singl...

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Published inScience (American Association for the Advancement of Science) Vol. 328; no. 5979; pp. 760 - 763
Main Authors Lee, Han-Ki, Yang, Yoosoo, Su, Zengliu, Hyeon, Changbong, Lee, Tae-Sun, Lee, Hong-Won, Kweon, Dae-Hyuk, Shin, Yeon-Kyun, Yoon, Tae-Young
Format Journal Article
LanguageEnglish
Published Washington, DC American Association for the Advancement of Science 07.05.2010
The American Association for the Advancement of Science
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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.
AbstractList 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.
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 Sytl 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.
In neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca super(2+) levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca super(2+)-triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca super(2+) sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca super(2+) level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca super(2+) levels and may function as a dynamic presynaptic Ca super(2+) sensor to control the probability of neurotransmitter release.
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. [PUBLICATION ABSTRACT]
In neurons, synaptotagmin1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca 2+ levels rise. However, in vitro reconstitution experiments have failed to recapitulate key characteristics of Ca 2+ -triggered membrane fusion. Using an in vitro single-vesicle fusion assay, we found that membrane-anchored Syt1 enhanced Ca 2+ -sensitivity and fusion speed. This stimulatory activity of membrane-anchored Syt1 dropped as the Ca 2+ level rose beyond physiological levels. Thus, Syt1 requires the membrane anchor to stimulate vesicle fusion at physiological Ca 2+ levels, and may function as a dynamic presynaptic Ca 2+ sensor to control the probability of neurotransmitter release.
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.
Author Yang, Yoosoo
Kweon, Dae-Hyuk
Lee, Han-Ki
Su, Zengliu
Lee, Tae-Sun
Hyeon, Changbong
Lee, Hong-Won
Shin, Yeon-Kyun
Yoon, Tae-Young
AuthorAffiliation 5 School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, South Korea
4 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, 4152 Molecular Biology Building, Ames, Iowa 50011, USA
3 Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 4400-746, South Korea
6 Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang 790-784, South Korea
2 Institute for the BioCentury, KAIST, Daejeon 305-701, South Korea
1 Department of Physics, KAIST, Daejeon 305-701, South Korea
AuthorAffiliation_xml – name: 3 Department of Genetic Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do 4400-746, South Korea
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Issue 5979
Keywords Sensitivity
Neuron
Calcium
Synaptic membrane
Plasma membrane
Synaptic vesicle
Stimulation
Synaptotagmin
Experimental study
In vitro
Thought
Presynaptic
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These authors contributed equally to this work.
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Snippet 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 neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca²₊ levels rise. However,...
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 neurons, synaptotagmin 1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca super(2+) levels rise....
In neurons, synaptotagmin1 (Syt1) is thought to mediate the fusion of synaptic vesicles with the plasma membrane when presynaptic Ca 2+ levels rise. However,...
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SubjectTerms Animals
Biochemistry
Biological and medical sciences
Calcium - metabolism
Cell membranes
Cellular biology
Fluorescence
Fundamental and applied biological sciences. Psychology
Imaging
Kinetics
Lipids
Magnesium - metabolism
Membrane Fusion
Membrane Lipids - metabolism
Membranes
Neurons
Neurotransmitter Agents - metabolism
Neurotransmitters
Phosphatidylinositol 4,5-Diphosphate - metabolism
Physiological stimulation
Proteins
Rats
rev genes
SNARE Proteins - metabolism
Synaptic Vesicles - physiology
Synaptotagmin I - chemistry
Synaptotagmin I - metabolism
Synaptotagmins
Vertebrates: nervous system and sense organs
Title Dynamic Ca²⁺-Dependent Stimulation of Vesicle Fusion by Membrane-Anchored Synaptotagmin 1
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