VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission.

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Title: VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission.
Authors: Raingo, Jesica, Khvotchev, Mikhail, Liu, Pei, Darios, Frederic, Li, Ying C, Ramirez, Denise M O, Adachi, Megumi, Lemieux, Philippe, Toth, Katalin, Davletov, Bazbek, Kavalali, Ege T
Source: Nature Neuroscience. May2012, Vol. 15 Issue 5, p738-745. 8p.
Subjects: Synaptic vesicles, Protein receptors, Synaptobrevin, Vesicles (Cytology), Neural transmission
Abstract: Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins. With the exception of synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion, the role of these SNAREs in neurotransmission is unclear. Here we show that in mice syb2 drives rapid Ca2+-dependent synchronous neurotransmission, whereas the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca2+-dependent asynchronous release. At inhibitory nerve terminals, up- or downregulation of VAMP4 causes a correlated change in asynchronous release. Biochemically, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25 that does not interact with complexins or synaptotagmin-1, proteins essential for synchronous neurotransmission. Optical imaging of individual synapses indicates that trafficking of VAMP4 and syb2 show minimal overlap. Taken together, these findings suggest that VAMP4 and syb2 diverge functionally, traffic independently and support distinct forms of neurotransmission. These results provide molecular insight into how synapses diversify their release properties by taking advantage of distinct synaptic vesicle-associated SNAREs. [ABSTRACT FROM AUTHOR]
Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission.
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  Data: <searchLink fieldCode="AR" term="%22Raingo%2C+Jesica%22">Raingo, Jesica</searchLink><br /><searchLink fieldCode="AR" term="%22Khvotchev%2C+Mikhail%22">Khvotchev, Mikhail</searchLink><br /><searchLink fieldCode="AR" term="%22Liu%2C+Pei%22">Liu, Pei</searchLink><br /><searchLink fieldCode="AR" term="%22Darios%2C+Frederic%22">Darios, Frederic</searchLink><br /><searchLink fieldCode="AR" term="%22Li%2C+Ying+C%22">Li, Ying C</searchLink><br /><searchLink fieldCode="AR" term="%22Ramirez%2C+Denise+M+O%22">Ramirez, Denise M O</searchLink><br /><searchLink fieldCode="AR" term="%22Adachi%2C+Megumi%22">Adachi, Megumi</searchLink><br /><searchLink fieldCode="AR" term="%22Lemieux%2C+Philippe%22">Lemieux, Philippe</searchLink><br /><searchLink fieldCode="AR" term="%22Toth%2C+Katalin%22">Toth, Katalin</searchLink><br /><searchLink fieldCode="AR" term="%22Davletov%2C+Bazbek%22">Davletov, Bazbek</searchLink><br /><searchLink fieldCode="AR" term="%22Kavalali%2C+Ege+T%22">Kavalali, Ege T</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. May2012, Vol. 15 Issue 5, p738-745. 8p.
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  Data: Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) proteins. With the exception of synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion, the role of these SNAREs in neurotransmission is unclear. Here we show that in mice syb2 drives rapid Ca2+-dependent synchronous neurotransmission, whereas the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca2+-dependent asynchronous release. At inhibitory nerve terminals, up- or downregulation of VAMP4 causes a correlated change in asynchronous release. Biochemically, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25 that does not interact with complexins or synaptotagmin-1, proteins essential for synchronous neurotransmission. Optical imaging of individual synapses indicates that trafficking of VAMP4 and syb2 show minimal overlap. Taken together, these findings suggest that VAMP4 and syb2 diverge functionally, traffic independently and support distinct forms of neurotransmission. These results provide molecular insight into how synapses diversify their release properties by taking advantage of distinct synaptic vesicle-associated SNAREs. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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