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. |