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Synaptic vesicle exocytosis is the biological process by which a synaptic vesicle fuses with the plasma membrane of the pre-synaptic axon terminal and releases its contents into the synaptic cleft. Before exocytosis, neurotransmitter-filled synaptic vesicles are docked at the plasma membrane and primed: exocytosis is triggered by calcium influx.
It is currently unknown how uniform is signalling at the first synapse of vision in vivo. Here, the authors show neighbouring PR1 (red) cones differ in contrast sensitivity and timing due to locally stochastic horizontal-cell feedback, thereby extending total dynamic range.
Synaptic vesicle fusion is essential for neuronal communication, yet its nanoscale sequence has not been directly confirmed. Here, the authors use timed in situ cryo-electron tomography to visualize the full fusion process and its link to vesicle resupply.
Syntaxin-1A, a SNARE protein mediating membrane fusion for neurotransmission, forms clusters with unclear functions. Using light-controlled clustering, the authors found that phase-separation-driven clusters, regulated by Munc18, suppress fusion, revealing a new phase-separation-based mechanism.
Defective neurotransmission is a hallmark of spinal muscular atrophy (SMA). Here, the authors show that local presynaptic Munc13-1synthesis is defective in SMA and that modification of the Munc13-1 mRNA rescues presynaptic architecture and excitability.
NSF hydrolyzes ATP to disassemble SNARE complexes. Here, the authors find NSF colocalizes with syntaxin nanodomains, reveal disassembly of syntaxin oligomers and other pre-fusion cis-SNARE complexes by NSF, and show how sequential hydrolysis drives disassembly.
Both full-collapse fusion and the more transient ‘kiss-and-run’ fusion are shown to occur at hippocampal synapses, with the kiss-and-run form involving vesicle shrinkage in between ‘kissing’ and ‘running’.
Following synaptic vesicle exocytosis, synaptotagmin 1 recruits a lipid signalling pathway within the presynaptic plasma membrane that drives local dynamin recruitment and membrane retrieval by endocytosis, thus maintaining membrane homeostasis.
In zebrafish, pioneer axons of the dorsal root ganglia require the release of synaptic-like vesicles to enter the spinal cord, suggesting that synaptic vesicles have a role in circuit formation ahead of synaptogenesis.
Super-resolution optical imaging of presynaptic terminals shows that a protein essential to all known forms of neurotransmitter release is clustered in small assemblies that likely correspond to release sites for synaptic vesicle fusion.
Ca2+-independent but voltage-dependent secretion is mediated by the voltage-gated calcium channel subunit CaV2.2, is enabled by SNARE machinery and results in release of ATP or neuropeptide Y.
