Neurexin-Neuroligin 1 regulates synaptic morphology and functions via the WAVE regulatory complex in Drosophila neuromuscular junction.
Neurexin-Neuroligin 1 regulates synaptic morphology and functions via the WAVE regulatory complex in Drosophila neuromuscular junction.
复制标题
Neurexin-Neuroligin 1 通过果蝇神经肌肉接头中的 WAVE 调节复合物调节突触形态和功能
作者：
Xing G;Li M;Sun Y;Rui M;Zhuang Y;Lv H;Han J;Jia Z;Xie W
神经胶素是突触后粘附分子，对突触后特化和突触功能至关重要。但神经配素功能的潜在分子机制仍不清楚。我们发现果蝇神经配素1（DNlg 1）通过WAVE调节复合物（WRC）介导的突触后肌动蛋白重组来调节突触结构和功能。DNlg 1，DNlg 2，或其突触前伙伴neurexin（DNS 2）的中断导致F-肌动蛋白的量急剧减少。进一步的研究表明，DNlg 1，而不是DNlg 2或DNlg 3，直接通过其C-末端相互作用受体序列与WRC相互作用。这种相互作用是将WRC募集到突触后膜以促进F-肌动蛋白组装所必需的。此外，DNlg 1和WRC之间的相互作用是必不可少的DNlg 1拯救DNlg 1突变体的形态和电生理缺陷。我们的研究结果揭示了一种新的机制，通过这种机制，DNrx-DNlg 1跨突触相互作用协调神经肌肉接头的结构和功能特性。
Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.