Septins Regulate Developmental Switching from Microdomain to Nanodomain Coupling of Ca2+ Influx to Neurotransmitter Release at a Central Synapse
| Autor: | Hong Xie, Lu-Yang Wang, Jamila Aitoubah, Cameron A. Ackerley, Giovanbattista Grande, William S. Trimble, Christopher W. Tsang, Yi Mei Yang, Michael J. Fedchyshyn |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Patch-Clamp Techniques
Neuroscience(all) Presynaptic Terminals CHO Cells Neurotransmission Biology In Vitro Techniques Septin Synaptic vesicle Models Biological Synaptic Transmission Article Antibodies MOLNEURO Cerebral Ventricles Synapse 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cricetulus GTP-Binding Protein Regulators Membrane Microdomains Microscopy Electron Transmission Cricetinae Animals Neurotransmitter Selenoproteins 030304 developmental biology Chelating Agents Mice Knockout 0303 health sciences Neurotransmitter Agents General Neuroscience Lipid microdomain Age Factors Excitatory Postsynaptic Potentials Cell biology Coupling (electronics) chemistry Animals Newborn SIGNALING Synapses Vesicular Glutamate Transport Protein 1 Calcium SYSNEURO Calyx of Held 030217 neurology & neurosurgery Brain Stem |
| Zdroj: | Neuron. (1):100-115 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/j.neuron.2010.06.003 |
| Popis: | SummaryNeurotransmitter release depends critically on close spatial coupling of Ca2+ entry to synaptic vesicles at the nerve terminal; however, the molecular substrates determining their physical proximity are unknown. Using the calyx of Held synapse, where “microdomain” coupling predominates at immature stages and developmentally switches to “nanodomain” coupling, we demonstrate that deletion of the filamentous protein Septin 5 imparts immature synapses with striking morphological and functional features reminiscent of mature synapses. This includes synaptic vesicles tightly localized to active zones, resistance to the slow Ca2+ buffer EGTA and a reduced number of Ca2+ channels required to trigger single fusion events. Disrupting Septin 5 organization acutely transforms microdomain to nanodomain coupling and potentiates quantal output in immature wild-type terminals. These observations suggest that Septin 5 is a core molecular substrate that differentiates distinct release modalities at the central synapse. |
| Databáze: | OpenAIRE |
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