2014 Jul 28. doi: 10.1111/jnc.12839. [Epub ahead of print]
Cannabinoid receptor 1 modulates the autophagic flux independent of mTOR- and BECLIN1-complex.
Abstract
Cannabinoid Receptor 1 (CB1) has been initially described as the receptor for Delta-9-Tetrahydrocannabinol in the central nervous system (CNS), mediating retrograde synaptic signaling of the endocannabinoid system. Beside its expression in various CNS regions, CB1 is ubiquituous in peripheral tissues, where it mediates, among other activities, the cell’s energy homeostasis. We sought to examine the role of CB1 in the context of the evolutionarily conserved autophagic machinery, a main constituent of the regulation of intracellular energy status. Manipulating CB1 by siRNA knockdown in mammalian cells caused an elevated autophagic flux, while the expression of autophagy-related genes remained unaltered. Pharmacological inhibition of CB1 activity using Rimonabant likewise caused an elevated autophagic flux, which was independent of the mammalian target of rapamycin complex 1 (mTOR), a major switch in the control of canonical autophagy. In addition, knocking down BECLIN1, the key-protein of the second canonical autophagy control complex, was insufficient to reduce the elevated autophagic flux induced by Rimonabant. Interestingly, lysosomal activity is not altered, suggesting a specific effect of CB1 on the regulation of autophagic flux. We conclude that CB1 activity affects the autophagic flux independently of the two major canonic regulation complexes controlling autophagic vesicle formation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
GPCR ; Autophagy; CB1; Peripheral; non-canonical
- PMID:
- 25066892
- [PubMed – as supplied by publisher]
