NIH VideoCast - Molecular mechanisms of neurotransmitter release

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Molecular mechanisms of neurotransmitter release

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Air date:	Monday, October 22, 2018, 12:00:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 406 (45 Live, 361 On-demand)
Category:	Neuroscience
Runtime:	01:10:14
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	NIH Neuroscience Series Seminar Nerve cells communicate by releasing the contents of neurotransmitter-bearing synaptic vesicles into the space between adjoining cells. This process depends on a handful of proteins that promote vesicle and nerve cell membrane fusion. The Brunger lab team uses structural and biophysical tools to capture this machinery at different stages of vesicle fusion. These structures then provide the framework for further investigations, using microscopy and live neurons, into the functional and dynamic aspects of the system. SNARE proteins, found in both nerve cell and vesicle membranes, set the stage for fusion by zipping together into a parallel, four-helix bundle that juxtaposes the two membranes. Brunger and his collaborators determined the first x-ray crystal structure of the neuronal SNARE complex, as well as the structures of other key components of the synaptic release machinery. Recently, the Brunger’s team visualized the SNARE complex bound to the Ca2+-sensor synaptotagmin-1 and to the regulator complexin, revealing two interfaces that are essential for fast synchronous release of neurotransmitters. The structure of this three-part complex suggests that it is in a primed and locked state. Action-potential-driven Ca2+ ions bind to the synaptotagmin proteins, unlock the complex, and trigger membrane fusion on a sub-millisecond timescale. After fusion has occurred, SNARE complexes are recycled by the ATPase NSF, which breaks down the SNARE complex into its individual components. The Brunger team visualized this molecular machine at near-atomic level and obtained the first glimpses of how this SNARE-recycling machine works. The SNARE complex resembles a rope with a left-handed twist, and NSF uses adapter proteins called SNAPs to grasp the “rope” in multiple places. The SNAPs wrap around the SNARE complex with a right-handed twist, suggesting that the disassembly occurs via a simple unwinding motion that frees the zipped SNARE proteins. The Brunger team is also using structural and functional studies to explore other machinery relevant to neurotransmitter release, such as factors involved in priming and pre-synaptic plasticity. Their research may one day provide new possibilities for targeting therapeutics to control neurotransmitter release. For more information go to https://neuroscience.nih.gov/neuroseries/Home.aspx

NLM Title:	Molecular mechanisms of neurotransmitter release / Axel Brunger.
Author:	Brünger, Axel T. National Institutes of Health (U.S.),
Publisher:
Abstract:	(CIT): NIH Neuroscience Series Seminar Nerve cells communicate by releasing the contents of neurotransmitter-bearing synaptic vesicles into the space between adjoining cells. This process depends on a handful of proteins that promote vesicle and nerve cell membrane fusion. The Brunger lab team uses structural and biophysical tools to capture this machinery at different stages of vesicle fusion. These structures then provide the framework for further investigations, using microscopy and live neurons, into the functional and dynamic aspects of the system. SNARE proteins, found in both nerve cell and vesicle membranes, set the stage for fusion by zipping together into a parallel, four-helix bundle that juxtaposes the two membranes. Brunger and his collaborators determined the first x-ray crystal structure of the neuronal SNARE complex, as well as the structures of other key components of the synaptic release machinery. Recently, the Brunger"s team visualized the SNARE complex bound to the Ca2+-sensor synaptotagmin-1 and to the regulator complexin, revealing two interfaces that are essential for fast synchronous release of neurotransmitters. The structure of this three-part complex suggests that it is in a primed and locked state. Action-potential-driven Ca2+ ions bind to the synaptotagmin proteins, unlock the complex, and trigger membrane fusion on a sub-millisecond timescale. After fusion has occurred, SNARE complexes are recycled by the ATPase NSF, which breaks down the SNARE complex into its individual components. The Brunger team visualized this molecular machine at near-atomic level and obtained the first glimpses of how this SNARE-recycling machine works. The SNARE complex resembles a rope with a left-handed twist, and NSF uses adapter proteins called SNAPs to grasp the "rope" in multiple places. The SNAPs wrap around the SNARE complex with a right-handed twist, suggesting that the disassembly occurs via a simple unwinding motion that frees the zipped SNARE proteins. The Brunger team is also using structural and functional studies to explore other machinery relevant to neurotransmitter release, such as factors involved in priming and pre-synaptic plasticity. Their research may one day provide new possibilities for targeting therapeutics to control neurotransmitter release.
Subjects:	Neurotransmitter Agents--metabolism SNARE Proteins--physiology
Publication Types:	Lecture Webcast

NLM Classification:	QV 126
NLM ID:	101737002
CIT Live ID:	28075
Permanent link:	https://videocast.nih.gov/watch=28075

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