A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching.
A novel Netrin-1-sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching.
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一种新的 Netrin-1 敏感机制促进轴突分支过程中局部 SNARE 介导的胞吐作用。
DOI：
10.1083/jcb.201311003
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发表时间：
2014-04-28
期刊：
影响因子：
--
通讯作者：
Gupton SL
中科院分区：
文献类型：
--
作者：
Winkle CC;McClain LM;Valtschanoff JG;Park CS;Maglione C;Gupton SL
Netrin-1介导的轴突分支期间的局部质膜扩张通过SNARE介导的囊泡融合的TRIM 9依赖性调节发生。发育轴突分支显着增加突触能力和神经元表面积。Netrin-1促进分支和突触发生，但Netrin-1刺激质膜扩张的机制尚不清楚。我们证明了SNARE介导的胞吐作用是轴突分支的先决条件，并确定E3泛素连接酶TRIM 9作为Netrin-1和胞吐SNARE机制在小鼠皮层神经元之间的关键催化链接。TRIM 9连接酶活性以Netrin依赖性方式促进SNARE介导的囊泡融合和轴突分支。我们鉴定了TRIM 9和Netrin-1受体DCC之间的直接相互作用以及TRIM 9和SNARE组分SNAP 25之间的Netrin-1敏感性相互作用。与SNAP 25的相互作用负调节SNARE介导的胞吐作用和轴突分支的Netrin-1的情况下。TRIM 9的缺失在体外提高了胞吐作用，并在体外和体内增加了轴突分支。我们的数据提供了一个新的模型，轴突分支的空间调控Netrin-1，其中局部质膜扩张发生通过TRIM 9依赖性调节SNARE介导的囊泡融合。
Localized plasma membrane expansion during axon branching mediated by Netrin-1 occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion. Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion.
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影响因子：
5.3
作者：
Dent, EW;Barnes, AM;Kalil, K
通讯作者：
Kalil, K
影响因子：
5.3
作者：
Goldman, Jennifer S.;Ashour, Mohammed A.;Kennedy, Timothy E.
通讯作者：
Kennedy, Timothy E.
影响因子：
3.9
作者：
Hamalainen, Riikka H;Avela, Kristiina;Lehesjoki, Anna-Elina
通讯作者：
Lehesjoki, Anna-Elina
影响因子：
11.8
作者：
Alexander, Mariam;Selman, Guillermo;Roy, Peter J.
通讯作者：
Roy, Peter J.
影响因子：
3.4
作者：
Cotrufo, Tiziana;Maria Andres, Rosa;Soriano, Eduardo
通讯作者：
Soriano, Eduardo