Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 41, Pages 10245-10256Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2139-08.2008
Keywords
p38 kinase; lactacystin; ubiquitin C-terminal hydrolase; CREB2; histone acetylation; synapsin
Categories
Funding
- NINDS NIH HHS [R01 NS019895, NS019895, R01 NS019895-25A1] Funding Source: Medline
Ask authors/readers for more resources
The neuropeptide Phe-Met-Arg-Phe-NH2 ( FMRFa) can induce transcription-dependent long-term synaptic depression (LTD) in Aplysia sensorimotor synapses. We investigated the role of the ubiquitin-proteasome system and the regulation of one of its components, ubiquitin C-terminal hydrolase (ap-uch), in LTD. LTD was sensitive to presynaptic inhibition of the proteasome and was associated with upregulation of ap-uch mRNA and protein. This upregulation appeared to be mediated by CREB2, which is generally regarded as a transcription repressor. Binding of CREB2 to the promoter region of ap-uch was accompanied by histone hyperacetylation, suggesting that CREB2 cannot only inhibit but also promote gene expression. CREB2 was phosphorylated after FMRFa, and blocking phospho CREB2 blocked LTD. In addition to changes in the expression of ap-uch, the synaptic vesicle-associated protein synapsin was downregulated in LTD in a proteasome- dependent manner. These results suggest that proteasome-mediated protein degradation is engaged in LTD and that CREB2 may act as a transcription activator under certain conditions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available