Publication Date

10-8-2008

Journal

J Neurosci. 2008 October 8; 28(41): 10245–10256.

Abstract

The neuropeptide Phe-Met-Arg-Phe-NH(2) (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.

Keywords

Acetylation, Acetylcysteine, Animals, Aplysia, Cells, Cultured, Coculture Techniques, Cyclic AMP Response Element-Binding Protein, Cysteine Proteinase Inhibitors, Down-Regulation, FMRFamide, Ganglia, Histones, Long-Term Synaptic Depression, Motor Neurons, Nerve Tissue Proteins, Neurons, Afferent, Phosphorylation, Promoter Regions, Genetic, Proteasome Endopeptidase Complex, Proteins, RNA, Messenger, Repressor Proteins, Synapsins, Synaptosomes, Ubiquitin, Ubiquitin Thiolesterase, Ubiquitination, Up-Regulation, p38 Mitogen-Activated Protein Kinases

Comments

PMCID: PMC2571080

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