Vesicular Synaptobrevin/VAMP2 Levels Guarded by AP180 Control Efficient Neurotransmission
| Autor: | Volker Haucke, Dmytro Puchkov, Georgi Tadeus, Tanja Maritzen, Christian Rosenmund, Martin Lehmann, Niclas Gimber, Gaga Kochlamazashvili, Benjamin R. Rost, Jan Schmoranzer, Seong Joo Koo |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Mice 129 Strain Vesicle-Associated Membrane Protein 2 Synaptobrevin Neuroscience(all) Endocytic cycle Mice Transgenic Biology Neurotransmission Hippocampus Synaptic Transmission Synaptic vesicle Exocytosis Mice Organ Culture Techniques Animals Humans Cells Cultured Mice Knockout VAMP2 General Neuroscience Excitatory Postsynaptic Potentials Endocytosis Cell biology Mice Inbred C57BL Protein Transport HEK293 Cells Biochemistry Monomeric Clathrin Assembly Proteins Excitatory postsynaptic potential Ap180 Female Synaptic Vesicles |
| Zdroj: | Neuron. 88(2):330-344 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2015.08.034 |
| Popis: | SummaryNeurotransmission depends on synaptic vesicle (SV) exocytosis driven by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex formation of vesicular synaptobrevin/VAMP2 (Syb2). Exocytic fusion is followed by endocytic SV membrane retrieval and the high-fidelity reformation of SVs. Syb2 is the most abundant SV protein with 70 copies per SV, yet, one to three Syb2 molecules appear to be sufficient for basal exocytosis. Here we demonstrate that loss of the Syb2-specific endocytic adaptor AP180 causes a moderate activity-dependent reduction of vesicular Syb2 levels, defects in SV reformation, and a corresponding impairment of neurotransmission that lead to excitatory/inhibitory imbalance, epileptic seizures, and premature death. Further reduction of Syb2 levels in AP180−/−/Syb2+/− mice results in perinatal lethality, whereas Syb2+/− mice partially phenocopy loss of AP180, indicating that reduced vesicular Syb2 levels underlie the observed defects in neurotransmission. Thus, a large vesicular Syb2 pool maintained by AP180 is crucial to sustain efficient neurotransmission and SV reformation. |
| Databáze: | OpenAIRE |
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