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Neuroscience Bulletin

, Volume 34, Issue 6, pp 1037–1046 | Cite as

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

  • Dan Wu
  • Zongbing Hao
  • Haigang RenEmail author
  • Guanghui WangEmail author
Original Article
  • 225 Downloads

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.

Keywords

VAPB Autophagy Beclin 1 ALS Autophagic flux LC3 

Notes

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.

Compliance with Ethical Standards

Conflict of interest

The authors declared that they have no conflict of interest.

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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical SciencesSoochow UniversitySuzhouChina

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