Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner.
Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner.
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VAPB 的缺失以 Beclin 1 依赖性方式调节自噬。
DOI：
10.1007/s12264-018-0276-9
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Wang Guanghui
中科院分区：
文献类型：
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作者：
Wu Dan;Hao Zongbing;Ren Haigang;Wang Guanghui
自噬是一种进化保守的自我降解过程，通过清除蛋白质聚集体和受损细胞器来维持细胞内环境的稳定。最近，囊泡相关膜蛋白相关蛋白B（VAP B），这是与肌萎缩侧索硬化症的家族形式，已被证明可以调节自噬。在本研究中，我们证明，敲低VAPB诱导beclin 1的表达上调，这促进了LC 3（微管相关蛋白轻链3）的转换和LC 3斑点的形成，而VAPB的过表达抑制这些过程。VAPB对beclin 1的调控是在转录水平上进行的。此外，VAPB的敲低增加了自噬通量，这促进了自噬底物p62和神经退行性疾病蛋白的降解。我们的研究提供的证据表明，VAPB的自噬调控与自噬起始因子beclin 1有关。
Autophagy is an evolutionarily-conserved self-degradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles. Recently, vesicle-associated membrane protein-associated protein B (VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3 (microtubule-associated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin 1 by VAPB was at the transcriptional level. Moreover, knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1.