Department of Physiology, McGill University, Montréal, QC H3G 1Y6, Canada.
Neuron. 2010 May 27;66(4):536-49. doi: 10.1016/j.neuron.2010.04.011.
Retrograde signaling is essential for coordinating the growth of synaptic structures; however, it is not clear how it can lead to modulation of cytoskeletal dynamics and structural changes at presynaptic terminals. We show that loss of retrograde bone morphogenic protein (BMP) signaling at the Drosophila larval neuromuscular junction (NMJ) leads to a significant reduction in levels of Rac GEF Trio and a diminution of transcription at the trio locus. We further find that Trio is required in motor neurons for normal structural growth. Finally, we show that transgenic expression of Trio in motor neurons can partially restore NMJ defects in larvae mutant for BMP signaling. Based on our findings, we propose a model in which a retrograde BMP signal from the muscle modulates GTPase activity through transcriptional regulation of Rac GEF trio, thereby regulating the homeostasis of synaptic growth at the NMJ.
逆行信号对于协调突触结构的生长至关重要;然而,目前尚不清楚它如何能够调节细胞骨架动力学和突触前末端的结构变化。我们发现,果蝇幼虫神经肌肉接点(NMJ)的逆行骨形态发生蛋白(BMP)信号丢失会导致 Rac GEF Trio 的水平显著降低,并使 trio 基因座的转录减少。我们进一步发现, Trio 在运动神经元中对于正常的结构生长是必需的。最后,我们发现,在 BMP 信号突变的幼虫中,运动神经元中转基因表达 Trio 可以部分恢复 NMJ 缺陷。基于我们的发现,我们提出了一个模型,其中来自肌肉的逆行 BMP 信号通过 Rac GEF trio 的转录调控来调节 GTPase 活性,从而调节 NMJ 处突触生长的动态平衡。