Proteasome limits plasticity-related signaling to the nucleus in the hippocampus. (20th November 2018)

• Record Type: Journal Article
• Authors: Vashisht, Anirudh; Bach, Svitlana V.; Fetterhoff, Dustin; Morgan, James W.; McGee, Maria; Hegde, Ashok N.
• Is Part Of: Neuroscience letters. Volume 687(2018)
• Page Start: 31
• Page End: 36
• Publication Date: 2018-11-20
• Subjects: Long-term potentiation -- Protein degradation -- Protein kinase -- Transcription factor -- Gene expression; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2018.09.017
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: We studied proteasomal regulation of nuclear signaling in synaptic plasticity. We used subthreshold long-term potentiation as our experimental model. We examined phosphorylation of cAMP-responsive element binding protein (CREB). Inhibition of the proteasome increased phosphorylated CREB (pCREB) in the nucleus. Blocking plasticity-related protein kinases prevented increase in pCREB. Abstract: Proteolysis by the ubiquitin-proteasome pathway has pleiotropic effects on both induction and maintenance of long-term synaptic plasticity. In this study, we examined the effect of proteasome inhibition on signaling to the nucleus during late-phase long-term potentiation. When a subthreshold L-LTP induction protocol was used, proteasome inhibition led to a significant increase in phosphorylated CREB (pCREB) in the nucleus. Inhibitors of cAMP-dependent protein kinase/protein kinase A, extracellular signal-regulated kinase and cGMP-dependent protein kinase/protein kinase G all blocked the proteasome-inhibition-mediated increase in nuclear pCREB after subthreshold stimulation. These results lay the groundwork for understanding a novel role for the proteasome in limiting signaling to the nucleus in the absence of adequate synaptic stimulation.