a Department of Biological Engineering, College of Chemistry, Chemical Engineering & Biotechnology , Donghua University , Shanghai , China.
b Department of Environmental Science and Engineering, College of Environmental Science & Engineering , Donghua University , Shanghai , China.
Autophagy. 2017 Oct 3;13(10):1679-1696. doi: 10.1080/15548627.2017.1353841. Epub 2017 Aug 18.
In addition to the canonical role in protein homeostasis, autophagy has recently been found to be involved in axonal dystrophy and neurodegeneration. Whether autophagy may also be involved in neural development remains largely unclear. Here we report that Mir505-3p is a crucial regulator for axonal elongation and branching in vitro and in vivo, through modulating autophagy in neurons. We identify that the key target gene of Mir505-3p in neurons is Atg12, encoding ATG12 (autophagy-related 12) which is an essential component of the autophagy machinery during the initiation and expansion steps of autophagosome formation. Importantly, axonal development is compromised in brains of mir505 knockout mice, in which autophagy signaling and formation of autophagosomes are consistently enhanced. These results define Mir505-3p-ATG12 as a vital signaling cascade for axonal development via the autophagy pathway, further suggesting the critical role of autophagy in neural development.
除了在蛋白质平衡中的规范作用外，自噬最近还被发现参与轴突萎缩和神经退行性变。自噬是否也可能参与神经发育在很大程度上仍不清楚。在这里，我们报告 Mir505-3p 通过调节神经元中的自噬，是体外和体内轴突伸长和分支的关键调节因子。我们确定 Mir505-3p 在神经元中的关键靶基因是 Atg12，其编码 ATG12（自噬相关 12），这是自噬体形成的起始和扩展步骤中自噬机制的必需成分。重要的是，mir505 敲除小鼠大脑中的轴突发育受损，其中自噬信号和自噬体的形成始终增强。这些结果定义 Mir505-3p-ATG12 为通过自噬途径进行轴突发育的重要信号级联，进一步表明自噬在神经发育中的关键作用。
