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Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner

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Abstract

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.

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Acknowledgements

This work was supported in part by the National Key R&D Program of China (2016YFC1306000), the National Natural Sciences Foundation of China (31330030, 31471012, and 81761148024), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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  1. Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215021, China

    Dan Wu, Zongbing Hao, Haigang Ren & Guanghui Wang

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  1. Dan Wu
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  2. Zongbing Hao
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Correspondence to Haigang Ren or Guanghui Wang.

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Wu, D., Hao, Z., Ren, H. et al. Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner. Neurosci. Bull. 34, 1037–1046 (2018). https://doi.org/10.1007/s12264-018-0276-9

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  • DOI: https://doi.org/10.1007/s12264-018-0276-9

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