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CB 1 -receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination.
- Source :
-
ELife [Elife] 2020 Sep 09; Vol. 9. Date of Electronic Publication: 2020 Sep 09. - Publication Year :
- 2020
-
Abstract
- Long-lasting forms of postsynaptic plasticity commonly involve protein synthesis-dependent structural changes of dendritic spines. However, the relationship between protein synthesis and presynaptic structural plasticity remains unclear. Here, we investigated structural changes in cannabinoid-receptor 1 (CB <subscript>1</subscript> )-mediated long-term depression of inhibitory transmission (iLTD), a form of presynaptic plasticity that involves a protein-synthesis-dependent long-lasting reduction in GABA release. We found that CB <subscript>1</subscript> -iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB <subscript>1</subscript> activation in hippocampal neurons resulted in increased ribosomal proteins and initiation factors, but decreased levels of proteins involved in regulation of the actin cytoskeleton, such as ARPC2 and WASF1/WAVE1, and presynaptic release. Moreover, while CB <subscript>1</subscript> -iLTD increased ubiquitin/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB <subscript>1</subscript> -iLTD. Thus, CB <subscript>1</subscript> -iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.<br />Competing Interests: HM, MB, BJ, PC No competing interests declared<br /> (© 2020, Monday et al.)
- Subjects :
- Actin-Related Protein 2-3 Complex metabolism
Animals
Female
Hippocampus chemistry
Hippocampus cytology
Hippocampus metabolism
Male
Rats
Rats, Sprague-Dawley
Wiskott-Aldrich Syndrome Protein Family metabolism
Long-Term Synaptic Depression physiology
Protein Biosynthesis physiology
Receptor, Cannabinoid, CB1 metabolism
Ubiquitination physiology
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 32902378
- Full Text :
- https://doi.org/10.7554/eLife.54812