Sakisaka Toshiaki, Yamamoto Yasunori, Mochida Sumiko, Nakamura Michiko, Nishikawa Kouki, Ishizaki Hiroyoshi, Okamoto-Tanaka Miki, Miyoshi Jun, Fujiyoshi Yoshinori, Manabe Toshiya, Takai Yoshimi
Division of Membrane Dynamics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
J Cell Biol. 2008 Oct 20;183(2):323-37. doi: 10.1083/jcb.200805150.
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.
来自突触前神经末梢的神经递质释放受可溶性 NSF 附着蛋白受体（SNARE）复合体介导的突触小泡融合调节。Tomosyn 通过其 C 末端囊泡相关膜蛋白（VAMP）样结构域（VLD）隔离 syntaxin-1，从而抑制 SNARE 复合体形成和神经递质释放。然而，在缺乏 tomosyn 的小鼠中，SNARE 复合体的形成意外减少。在本研究中，我们证明 tomosyn 的 N 末端 WD-40 重复结构域催化 SNARE 复合体的寡聚化。将 tomosyn 的 N 末端 WD-40 重复结构域显微注射到神经元中可阻止刺激引起的乙酰胆碱释放。因此，除了 C 末端 VLD 的抑制活性外，tomosyn 还通过 N 末端 WD-40 重复结构域催化 SNARE 复合体的寡聚化来抑制神经递质释放。
Zotero 插件
