CB1-receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination
Male
0301 basic medicine
presynaptic
protein synthesis
QH301-705.5
Science
ubiquitination
Hippocampus
Actin-Related Protein 2-3 Complex
Rats, Sprague-Dawley
03 medical and health sciences
Receptor, Cannabinoid, CB1
Animals
Biology (General)
Long-Term Synaptic Depression
Q
R
Ubiquitination
cannabinoid
structural plasticity
Rats
Wiskott-Aldrich Syndrome Protein Family
3. Good health
Protein Biosynthesis
Medicine
Female
Neuroscience
DOI:
10.7554/elife.54812
Publication Date:
2020-09-09T12:00:33Z
AUTHORS (4)
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 (CB1)-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 CB1-iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB1activation 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 CB1-iLTD increased ubiquitin/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB1-iLTD. Thus, CB1-iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.
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CITATIONS (22)
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