2014
DOI: 10.1002/anie.201406359
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The Molecular Machinery of Neurotransmitter Release (Nobel Lecture)

Abstract: The most important property of synaptic transmission is its speed, which is crucial for the overall workings of the brain. In his Nobel Lecture, T. C. Südhof explains how the synaptic vesicle and the plasma membrane undergo rapid fusion during neurotransmitter release and how this process is spatially organized, such that opening of Ca(2+) -channels allows rapid translation of the entering Ca(2+) signal into a fusion event.

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Cited by 155 publications
(154 citation statements)
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References 197 publications
(261 reference statements)
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“…Mammalian Munc18 and the C. elegans homolog UNC-18 mediate signal-regulated NT and NP secretion by interacting with SNARE proteins and promoting the docking, priming, and exocytosis of synaptic vesicles (SVs) and DCVs (48)(49)(50)(51). In the calyx of Held auditory synapse, cPKCs transmit Ca 2ϩ and DAG signals by phosphorylating Ser or Thr in the 3a domain of Munc18 (13,(52)(53)(54)(55)(56).…”
Section: Pkc-2 Links Thermosensory Signals To Learned Behaviormentioning
confidence: 99%
“…Mammalian Munc18 and the C. elegans homolog UNC-18 mediate signal-regulated NT and NP secretion by interacting with SNARE proteins and promoting the docking, priming, and exocytosis of synaptic vesicles (SVs) and DCVs (48)(49)(50)(51). In the calyx of Held auditory synapse, cPKCs transmit Ca 2ϩ and DAG signals by phosphorylating Ser or Thr in the 3a domain of Munc18 (13,(52)(53)(54)(55)(56).…”
Section: Pkc-2 Links Thermosensory Signals To Learned Behaviormentioning
confidence: 99%
“…These proteins exist as several splice variants or isoforms, some of which also operate at intracellular membrane-trafficking steps. However, because many of them appear to be functionally interchangeable, the physiological differences, if any, are yet not fully understood (21). SNAP-25 is essential for stimulus-dependent exocytosis, and disruption of the gene results in death at birth (46).…”
Section: (E and F) Hypothalamic Pstat3 Is Decreased In All Experimentmentioning
confidence: 99%
“…In excitable cells, the release of messenger molecules is a consequence of regulated membrane fusion and involves soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAREs) (20,21), including synaptosomal-associated protein of 25 kDa (SNAP-25). SNAP-25 is expressed as two developmentally regulated and alternatively spliced isoforms, SNAP-25a and SNAP-25b, which differ in only 9 of 206 amino acids (22,23).…”
mentioning
confidence: 99%
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“…Numerous proteins are recruited to the presynaptic space to execute a highly controlled and precise mechanism, resulting in the liberation of neurotransmitters to the synaptic cleft. Central components of the process are the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins: syntaxin-1A (STX1A), VAMP2 (synaptobrevin-2), and synaptosome-associated protein of 25 kDa (SNAP25), which fold into a stable four-helix bundle that brings together vesicle and plasma membranes, driving membrane fusion (1)(2)(3)(4). Other important players are complexin, Munc18-1, Munc13, and a collection of proteins that share a common structural motif: the C2 domain (5,6).…”
mentioning
confidence: 99%