Yang Yi, Xu Kedi, Koike Tatsuro, Zheng Xiaoxiang
Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou, P.R. China.
Autophagy. 2008 Feb;4(2):243-5. doi: 10.4161/auto.5431. Epub 2007 Dec 14.
Autophagy has been linked to various human diseases, including many neurodegenerative disorders. The induction of autophagy has been detected in degenerating neurites initiated by different experimental paradigms and hence is of major interest. Axonal and dendritic degeneration was significantly delayed either by the application of the autophagy inhibitor 3-methyladenine (3-MA) or by knocking down the key autophagy-related genes Atg7 and Beclin 1. In addition, Tomato-LC3-labelled autophagosomes accumulate in neuritic beadings of PC12 cells during nerve growth factor (NGF) deprivation, which might be due to the failure of neurite transport. However, little is known about routes and dynamics of autophagosomes in the neurites of living cells. Here, we further demonstrate that LC3-labelled small autophagosomes are motile and move along the neurites of PC12 cells in both anterograde and retrograde directions after serum deprivation. The autophagosomes paused, re-started, and sometimes changed directions. These results provide valuable insight into neuritic transport of autophagosomes and imply a close relationship between the autophagic process and neurite degeneration.
自噬与多种人类疾病相关,包括许多神经退行性疾病。在由不同实验范式引发的退化神经突中已检测到自噬的诱导,因此备受关注。应用自噬抑制剂3 - 甲基腺嘌呤(3 - MA)或敲低关键的自噬相关基因Atg7和Beclin 1,均可显著延迟轴突和树突的退化。此外,在神经生长因子(NGF)剥夺期间,番茄 - LC3标记的自噬体在PC12细胞的神经突珠中积累,这可能是由于神经突运输失败所致。然而,关于活细胞神经突中自噬体的途径和动态知之甚少。在这里,我们进一步证明,血清剥夺后,LC3标记的小自噬体具有运动性,并沿PC12细胞的神经突在顺行和逆行方向移动。自噬体暂停、重新启动,有时还会改变方向。这些结果为自噬体的神经突运输提供了有价值的见解,并暗示自噬过程与神经突退化之间存在密切关系。