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Publication : Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release.

First Author  Sakisaka T Year  2008
Journal  J Cell Biol Volume  183
Issue  2 Pages  323-37
PubMed ID  18936251 Mgi Jnum  J:140649
Mgi Id  MGI:3814264 Doi  10.1083/jcb.200805150
Citation  Sakisaka T, et al. (2008) Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release. J Cell Biol 183(2):323-37
abstractText  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.
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