Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011570 (
depression
)
172,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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
1
)-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
1
-iLTD in acute rat hippocampal slices was associated with protein synthesis-dependent presynaptic structural changes. Using proteomics, we determined that CB
1
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
1
-iLTD increased
ubiquitin
/proteasome activity, ubiquitination but not proteasomal degradation was critical for structural and functional presynaptic CB
1
-iLTD. Thus, CB
1
-iLTD relies on both protein synthesis and ubiquitination to elicit structural changes that underlie long-term reduction of GABA release.
...
PMID:CB
1
-receptor-mediated inhibitory LTD triggers presynaptic remodeling via protein synthesis and ubiquitination. 3290 78
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