Drosophila Neuroligin 1 Promotes Growth and Postsynaptic Differentiation at Glutamatergic Neuromuscular Junctions
Drosophila Neuroligin 1 Promotes Growth and Postsynaptic Differentiation at Glutamatergic Neuromuscular Junctions
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DOI：
10.1016/j.neuron.2010.05.020
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发表时间：
2010-06-10
期刊：
影响因子：
16.2
通讯作者：
Aberle, Hermann
中科院分区：
文献类型：
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作者：
Banovic, Daniel;Khorramshahi, Omid;Aberle, Hermann
突触前和突触后区域的精确并置是所有神经元回路的基本特性。体外实验表明，神经连接素和神经毒素在这一过程中起着关键的调节作用。在遗传筛选中，我们恢复了果蝇神经连接素1（dnIg 1）的几个突变等位基因，导致神经肌肉接头（NMJ）的终扣数量严重减少。与突触数量减少的雅阁一致，这些NMJ显示突触传递减少。此外，缺乏突触后DNIg 1导致突触后谷氨酸受体，支架蛋白和突触下膜的积累不足，而增加DNIg 1通过其胞质结构域触发异位突触后分化。DNIg 1形成邻近突触后密度的离散簇。这些簇的形成依赖于突触前果蝇神经毒素（DNXin）。然而，DNIgl结合不是DNIgl功能的绝对要求。相反，其他信号成分可能参与DNIg 1跨突触功能，与DNIg 1细胞外结构域，但也由胞质结构域组织的基本相互作用。
Precise apposition of presynaptic and postsynaptic domains is a fundamental property of all neuronal circuits. Experiments in vitro suggest that Neuroligins and Neurexins function as key regulatory proteins in this process. In a genetic screen, we recovered several mutant alleles of Drosophila neuroligin 1 (dnIg1) that cause a severe reduction in bouton numbers at neuromuscular junctions (NMJs). In accord with reduced synapse numbers, these NMJs show reduced synaptic transmission. Moreover, lack of postsynaptic DNIg1 leads to deficits in the accumulation of postsynaptic glutamate receptors, scaffold proteins, and subsynaptic membranes, while increased DNIg1 triggers ectopic postsynaptic differentiation via its cytoplasmic domain. DNIg1 forms discrete clusters adjacent to postsynaptic densities. Formation of these clusters depends on presynaptic Drosophila Neurexin (DNrx). However, DNrx binding is not an absolute requirement for DNIg1 function. Instead, other signaling components are likely involved in DNIg1 transsynaptic functions, with essential interactions organized by the DNIg1 extracellular domain but also by the cytoplasmic domain.