A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection.

A screen of cell-surface molecules identifies leucine-rich repeat proteins as key mediators of synaptic target selection.
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DOI:
10.1016/j.neuron.2008.07.037
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发表时间:
2008-09-25
期刊:
影响因子:
16.2
通讯作者:
Zinn K
Zinn K
中科院分区:
医学1区
文献类型:
--
作者:
Kurusu M;Cording A;Taniguchi M;Menon K;Suzuki E;Zinn K

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在果蝇胚胎和幼虫中,少数已识别的运动神经元以高度刻板的模式支配身体壁肌肉。尽管基因筛查已经确定了该系统中轴突引导和突触发生所需的许多蛋白质,但对肌肉纤维被定义为特定运动轴突靶向的机制知之甚少。为了确定潜在的靶标,我们筛选了410个编码细胞表面和分泌蛋白的基因,寻找那些在所有肌肉纤维上过度表达会导致运动轴突发生靶向错误的基因。已鉴定出30个这样的基因,其中一些是编码蛋白质的大基因家族的成员,其胞外结构域包含富含亮氨酸的重复序列(LRR),这是蛋白质相互作用的模块。通过操纵肌肉12中的基因表达,我们发现四个LRR蛋白参与了这块肌肉作为Rp5运动神经元适当突触靶点的选择。
In Drosophila embryos and larvae, a small number of identified motor neurons innervate body wall muscles in a highly stereotyped pattern. Although genetic screens have identified many proteins that are required for axon guidance and synaptogenesis in this system, little is known about the mechanisms by which muscle fibers are defined as targets for specific motor axons. To identify potential target labels, we screened 410 genes encoding cell-surface and secreted proteins, searching for those whose overexpression on all muscle fibers causes motor axons to make targeting errors. Thirty such genes were identified, and a number of these were members of a large gene family encoding proteins whose extracellular domains contain leucine-rich repeat (LRR) sequences, which are protein interaction modules. By manipulating gene expression in muscle 12, we showed that four LRR proteins participate in the selection of this muscle as the appropriate synaptic target for the RP5 motor neuron.
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