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 in | Science (American Association for the Advancement of Science) Vol. 328; no. 5979; pp. 760 - 763 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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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. |
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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 – name: 5 School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, South Korea – name: 2 Institute for the BioCentury, KAIST, Daejeon 305-701, South Korea – name: 4 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, 4152 Molecular Biology Building, Ames, Iowa 50011, USA – name: 1 Department of Physics, KAIST, Daejeon 305-701, South Korea – name: 6 Division of Integrative Biosciences and Biotechnology, POSTECH, Pohang 790-784, South Korea |
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Keywords | Sensitivity Neuron Calcium Synaptic membrane Plasma membrane Synaptic vesicle Stimulation Synaptotagmin Experimental study In vitro Thought Presynaptic |
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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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