SNARE Protein Recycling by aSNAP and bSNAP Supports Synaptic Vesicle Priming

• Published in: Neuron (Cambridge, Mass.) Vol. 68; no. 3; pp. 473 - 487
• Main Authors: Burgalossi, Andrea, Jung, Sangyong, Meyer, Guido, Jockusch, Wolf J, Jahn, Olaf, Taschenberger, Holger, O'Connor, Vincent M, Nishiki, Tei-Ichi, Takahashi, Masami, Brose, Nils, Rhee, Jeong-Seop
• Format: Journal Article
• Language: English
• Published: 04.11.2010
• Subjects: Adenosinetriphosphatase
• ISSN: 0896-6273
• DOI: 10.1016/j.neuron.2010.09.019

Neurotransmitter release proceeds by Ca super(2+)-triggered, SNARE-complex-dependent synaptic vesicle fusion. After fusion, the ATPase NSF and its cofactors a- and bSNAP disassemble SNARE complexes, thereby recycling individual SNAREs for subsequent fusion reactions. We examined the effects of genetic perturbation of a- and bSNAP expression on synaptic vesicle exocytosis, employing a new Ca super(2+) 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 Ca super(2+) 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 a- and bSNAP 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.