The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

中文翻译：

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骨骼肌和末梢雪旺细胞中的脚手架蛋白Grb2相关的Binder-1调节产后神经肌肉突触的成熟。

脊椎动物神经肌肉接头（NMJ）被认为是由运动轴突末端，肌肉终板和包裹运动轴突末端的Schwann末端细胞组成的“三联突触”。神经调节蛋白1（NRG1）-ErbB2信号通路在NMJ的发展中发挥重要作用。我们以前显示，NRG1诱导的周围神经髓鞘形成需要Grb2相关的粘合剂1（Gab1），受体酪氨酸激酶信号传导的支架介质。在这里，我们使用肌肉特定的条件性Gab1基因敲除小鼠确定了Gab1在NMJ发育中的作用。突变小鼠显示出NMJ的出生后延迟。此外，gab1的选择性损失Schwann末梢细胞中的基因产生延迟的突触消除和运动终板的异常形态，这表明适当的NMJ发育需要肌肉和末梢Schwann细胞中的Gab1。末梢雪旺细胞中的Gab1似乎在突触消除过程中调节末梢雪旺细胞的数量和过程伸长。但是，Gab2基因敲除小鼠在NMJ的发育中未显示任何缺陷。考虑到Gab1在产后外周神经髓鞘形成中的作用，我们的发现表明Gab1是外周神经肌肉系统产后发育过程中NRG1信号的多效性和重要组成部分。