VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission
| Autor: | Jesica Raingo, Denise M.O. Ramirez, Ying C. Li, Mikhail Khvotchev, Ege T. Kavalali, Megumi Adachi, Frédéric Darios, Katalin Tóth, Pei Liu, Philippe Lemieux, Bazbek Davletov |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Vesicle fusion
Patch-Clamp Techniques Synaptosomal-Associated Protein 25 Vesicle-Associated Membrane Protein 2 Syntaxin 1 Biology Neurotransmission Transfection Synaptic vesicle Hippocampus Synaptic Transmission Article Ammonium Chloride R-SNARE Proteins Rats Sprague-Dawley Mice Animals Humans Microscopy Immunoelectron Egtazic Acid Cells Cultured 6-Cyano-7-nitroquinoxaline-2 3-dione Mice Knockout Neurons Analysis of Variance VAMP2 General Neuroscience Valine Electric Stimulation Transport protein Cell biology Rats Protein Transport Animals Newborn Inhibitory Postsynaptic Potentials Gene Knockdown Techniques Mutation Synapses Calcium RNA Interference Synaptic Vesicles Cholecystokinin SNARE Proteins Neuroscience Excitatory Amino Acid Antagonists Protein Binding |
| Zdroj: | Nature neuroscience |
| ISSN: | 1097-6256 |
| Popis: | The authors show that the SNARE protein VAMP4 acts to maintain calcium-dependent asynchronous synaptic vesicle release. These findings suggest that VAMP4 is functionally distinct from synaptobrevin2, which primarily drives fast, synchronous release. 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. |
| Databáze: | OpenAIRE |
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