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Neuron. 2006 Aug 3;51(3):303-15.

Antagonistic regulation of synaptic vesicle priming by Tomosyn and UNC-13.

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1
Department of Molecular Biology, Massachusetts General Hospital, Simches Research Building, Seventh Floor, 185 Cambridge Street, Boston, Massachusetts 02114, USA.

Abstract

Priming of synaptic vesicles (SVs) is essential for synaptic transmission. UNC-13 proteins are required for priming. Current models propose that UNC-13 stabilizes the open conformation of Syntaxin, in which the SNARE helix is available for interactions with Synaptobrevin and SNAP-25. Here we show that Tomosyn inhibits SV priming. Tomosyn contains a SNARE motif, which forms an inhibitory SNARE complex with Syntaxin and SNAP-25. Mutants lacking Tomosyn have increased synaptic transmission, an increased pool of primed vesicles, and increased abundance of UNC-13 at synapses. Behavioral, imaging, and electrophysiological studies suggest that SV priming was reconstituted in unc-13 mutants by expressing a constitutively open mutant Syntaxin, or by mutations eliminating Tomosyn. Thus, priming is modulated by the balance between Tomosyn and UNC-13, perhaps by regulating the availability of open-Syntaxin. Even when priming was restored, synaptic transmission remained defective in unc-13 mutants, suggesting that UNC-13 is also required for other aspects of secretion.

PMID:
16880125
DOI:
10.1016/j.neuron.2006.06.025
[Indexed for MEDLINE]
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