The ubiquitin-proteasome system is necessary for long-term synaptic depression in Aplysia.
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.
Fioravante
Diasinou
D
Department of Neurobiology and Anatomy, W. M. Keck Center for the Neurobiology of Learning and Memory, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Liu
Rong-Yu
RY
Byrne
John H
JH
D000107:Acetylation; D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001048:Aplysia / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D019835:FMRFamide / Q000494:pharmacology; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009046:Motor Neurons / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000502:physiology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D016704:Synapsins / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C097204:ApCREB2 protein, Aplysia californica; D017362:Cyclic AMP Response Element-Binding Protein; D015853:Cysteine Proteinase Inhibitors; D006657:Histones; D009419:Nerve Tissue Proteins; D061988:Proteasome Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D016704:Synapsins; D025801:Ubiquitin; C067713:lactacystin; D019835:FMRFamide; D048051:p38 Mitogen-Activated Protein Kinases; D043222:Ubiquitin Thiolesterase; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine