SNARE Protein Recycling by αSNAP and βSNAP Supports Synaptic Vesicle Priming

被引:75
作者
Burgalossi, Andrea [1 ]
Jung, Sangyong [1 ]
Meyer, Guido [1 ]
Jockusch, Wolf J. [1 ]
Jahn, Olaf [2 ,3 ]
Taschenberger, Holger [5 ]
O'Connor, Vincent M. [4 ]
Nishiki, Tei-ichi [6 ]
Takahashi, Masami [7 ]
Brose, Nils [1 ]
Rhee, Jeong-Seop [1 ]
机构
[1] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075 Gottingen, Germany
[2] Max Planck Inst Expt Med, Prote Grp, D-37075 Gottingen, Germany
[3] Max Planck Inst Expt Med, DFG CMPB, D-37075 Gottingen, Germany
[4] Max Planck Inst Brain Res, Dept Neurochem, D-60528 Frankfurt, Germany
[5] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany
[6] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008558, Japan
[7] Kitasato Univ, Sch Med, Dept Biochem, Kanagawa 2288555, Japan
关键词
ETHYLMALEIMIDE-SENSITIVE FACTOR; NEUROTRANSMITTER RELEASE; TRANSMITTER RELEASE; MEMBRANE-FUSION; ASYNCHRONOUS RELEASE; HIPPOCAMPAL-NEURONS; NEUROMUSCULAR-JUNCTION; SYNCHRONOUS RELEASE; SECRETORY VESICLES; SYNAPTOTAGMIN-I;
D O I
10.1016/j.neuron.2010.09.019
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neurotransmitter release proceeds by Ca2+-triggered, SNARE-complex-dependent synaptic vesicle fusion. After fusion, the ATPase NSF and its cofactors alpha- and beta SNAP disassemble SNARE complexes, thereby recycling individual SNAREs for subsequent fusion reactions. We examined the effects of genetic perturbation of alpha- and beta SNAP expression on synaptic vesicle exocytosis, employing a new Ca2+ uncaging protocol to study synaptic vesicle trafficking, priming, and fusion in small glutamatergic synapses of hippocampal neurons. By characterizing this protocol, we show that synchronous and asynchronous transmitter release involve different Ca2+ sensors and are not caused by distinct releasable vesicle pools, and that tonic transmitter release is due to ongoing priming and fusion of new synaptic vesicles during high synaptic activity. Our analysis of alpha- and beta SNAP deletion mutant neurons shows that the two NSF cofactors support synaptic vesicle priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity.
引用
收藏
页码:473 / 487
页数:15
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