Close association of polarization and LC3, a marker of autophagy, in axon determination in mouse hippocampal neurons.
Close association of polarization and LC3, a marker of autophagy, in axon determination in mouse hippocampal neurons.
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在小鼠海马神经元的轴突测定中，极化与自噬标记物 LC3 密切相关。
DOI：
10.1016/j.expneurol.2022.114112
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
K.
中科院分区：
文献类型：
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作者：
Segi;N.;Ozaki;T.;Suzuki;Y.;Ouchida;J.;Imagama;S;Kadomatsu;K.;Sakamoto;K.
自噬-溶酶体途径是细胞内细胞器、大分子和微生物的细胞清除系统。细胞不仅要维持自身的稳态，而且要实现更活跃的细胞过程，如分化，这是必不可少的。因此，自噬-溶酶体途径的损伤或破坏导致多种人类疾病，从几种类型的神经退行性疾病到恶性肿瘤。在伸长的轴突中，自噬优先发生在生长锥，并且自噬的破坏与中枢神经系统损伤后轴突再生的能力丧失密切相关。然而，自噬在发育神经元中的作用仍然难以捉摸。特别是，自噬是否参与轴突树突的决定在很大程度上是不清楚的。利用原代培养的小鼠胚胎海马神经元，我们在这里显示了极化分布的自噬体之间的小突起的神经元在第2阶段。对来自GFP-LC 3转基因小鼠的神经元的延时观察表明，“LC 3浪涌”-即，自噬标记物LC 3的快速积累在一个小的过程中持续数小时，使神经元分化为轴突。此外，海藻糖和巴弗洛霉素对自噬的药理学激活和抑制分别加速和延迟了轴突的确定。总之，我们的研究结果揭示了LC 3（自噬的标志物）与发育中神经元轴突决定之间的密切联系。
The autophagy-lysosome pathway is a cellular clearance system for intracellular organelles, macromolecules and microorganisms. It is indispensable for cells not only to maintain their homeostasis but also to achieve more active cellular processes such as differentiation. Therefore, impairment or disruption of the autophagy-lysosome pathway leads to a wide spectrum of human diseases, ranging from several types of neurodegenerative diseases to malignancies. In elongating axons, autophagy preferentially occurs at growth cones, and disruption of autophagy is closely associated with incapacity for axonal regeneration after injury in the central nervous system. However, the roles of autophagy in developing neurons remain elusive. In particular, whether autophagy is involved in axon–dendrite determination is largely unclear. Using primary cultured mouse embryonic hippocampal neurons, we here showed the polarized distribution of autophagosomes among minor processes of neurons at stage 2. Time-lapse observation of neurons from GFP-LC3 transgenic mice demonstrated that an “LC3 surge”—i.e., a rapid accumulation of autophagic marker LC3 that continues for several hours in one minor process—proceeded the differentiation of neurons into axons. In addition, pharmacological activation and inhibition of autophagy by trehalose and bafilomycin, respectively, accelerated and delayed axonal determination. Taken together, our findings revealed the close association between LC3, a marker of autophagy, and axon determination in developing neurons.