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UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans 期刊论文

编号：

1431da68-0b50-4030-948a-ba7d2af855a0
作者：

Park, Seungmee#^[1,3]Bin, NaRyum^[1,3];Yu, Bin^[6];Wong, Raymond^[3,4];Sitarska, Ewa^[7,9];Sugita, Kyoko^[2];Ma, Ke(马可)^[1,10]Xu, Junjie^[7,8,9];Tien, ChiWei^[1,3];Algouneh, Arash^[1,3];Turlova, Ekaterina^[3,6];Wang, Siyan^[1];Siriya, Pranay^[1];Shahid, Waleed^[1];Kalia, Lorraine^[9];Feng, ZhongPing^[3];Monnier, Philippe P.^[2,3,11];Sun, HongShuo^[3,4];Zhen, Mei^[3,5,12];Gao, Shangbang^[6];Rizo, Josep^[7,8,9];Sugita, Shuzo*^[1,3]
语种：

英文
期刊：

JOURNAL OF NEUROSCIENCE ISSN：0270-6474 2017 年 37 卷 36 期 (8797 - 8815) ; SEP 6
收录：
关键词：

C. elegans exocytosis membrane fusion Munc18 SNARE synapse
摘要：

Munc18-1/UNC-18 is believed to prime SNARE-mediated membrane fusion, yet the underlying mechanisms remain enigmatic. Here, we examine how potential gain-of-function mutations of Munc18-1/UNC-18 affect locomotory behavior and synaptic transmission, and how Munc18-1-mediated priming is related to Munc13-1/UNC-13 and Tomosyn/TOM-1, positive and negative SNARE regulators, respectively. We show that a Munc18-1(P335A)/UNC-18(P334A) mutation leads to significantly increased locomotory activity and acetylcholine release in Caenorhabditis elegans, as well as enhanced synaptic neurotransmission in cultured mammalian neurons. Importantly, similar to tom-1 null mutants, unc-18(P334A) mutants partially bypass the requirement of UNC-13. Moreover, unc-18( P334A) and tom-1 null mutations confer a strong synergy in suppressing the phenotypes of unc-13 mutants. Through biochemical experiments, we demonstrate that Munc18-1( P335A) exhibits enhanced activity in SNARE complex formation as well as in binding to the preformed SNARE complex, and partially bypasses the Munc13-1 requirement in liposome fusion assays. Our results indicate that Munc18-1/UNC-18 primes vesicle fusion downstream of Munc13-1/UNC-13 by templating SNARE complex assembly and acts antagonistically with Tomosyn/TOM-1.
推荐引用方式
GB/T 7714：

Park Seungmee,Bin Na-Ryum,Yu Bin, et al. UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans [J].JOURNAL OF NEUROSCIENCE,2017,37(36):8797-8815.
APA：

Park Seungmee,Bin Na-Ryum,Yu Bin,Wong Raymond,&Sugita Shuzo.(2017).UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans .JOURNAL OF NEUROSCIENCE,37(36):8797-8815.
MLA：

Park Seungmee, et al. "UNC-18 and Tomosyn Antagonistically Control Synaptic Vesicle Priming Downstream of UNC-13 in Caenorhabditis elegans" .JOURNAL OF NEUROSCIENCE 37,36(2017):8797-8815.
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