Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215021, China.
Neurosci Bull. 2018 Dec;34(6):1037-1046. doi: 10.1007/s12264-018-0276-9. Epub 2018 Aug 24.
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.
自噬是一种进化上保守的自我降解过程，通过消除蛋白质聚集体和受损的细胞器来维持细胞内环境的稳定。最近，与家族性肌萎缩侧索硬化症相关的囊泡相关膜蛋白相关蛋白 B (VAPB) 已被证明可以调节自噬。在本研究中，我们证明了 VAPB 的敲低诱导了 beclin 1 表达的上调，促进了 LC3（微管相关蛋白轻链 3）的转化和 LC3 斑点的形成，而 VAPB 的过表达则抑制了这些过程。VAPB 对 beclin 1 的调节是在转录水平上进行的。此外，VAPB 的敲低增加了自噬流，促进了自噬底物 p62 和神经退行性疾病蛋白的降解。我们的研究提供了证据，表明 VAPB 对自噬的调节与自噬起始因子 beclin 1 有关。
