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Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release
Correspondence to Y. Takai: ytakai{at}med.kobe-u.ac.jp
Neurotransmitter release from presynaptic nerve terminals is regulated by soluble NSF attachment protein receptor (SNARE) complex–mediated synaptic vesicle fusion. Tomosyn inhibits SNARE complex formation and neurotransmitter release by sequestering syntaxin-1 through its C-terminal vesicle-associated membrane protein (VAMP)–like domain (VLD). However, in tomosyn-deficient mice, the SNARE complex formation is unexpectedly decreased. In this study, we demonstrate that the N-terminal WD-40 repeat domain of tomosyn catalyzes the oligomerization of the SNARE complex. Microinjection of the tomosyn N-terminal WD-40 repeat domain into neurons prevented stimulated acetylcholine release. Thus, tomosyn inhibits neurotransmitter release by catalyzing oligomerization of the SNARE complex through the N-terminal WD-40 repeat domain in addition to the inhibitory activity of the C-terminal VLD.
Abbreviations used in this paper: Ab, antibody; CSM, crude synaptic membrane; EPSP, excitatory postsynaptic potential; ES, embryonic stem; Lgl, lethal giant larvae; LTP, long-term potentiation; MBP, maltose-binding protein; PPF, paired-pulse facilitation; SCG, superior cervical ganglion; VAMP, vesicle-associated membrane protein; VLD, VAMP-like domain.
© 2008 Sakisaka et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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