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Details

Autor(en) / Beteiligte
Titel
Proteasome limits plasticity-related signaling to the nucleus in the hippocampus
Ist Teil von
  • Neuroscience letters, 2018-11, Vol.687, p.31-36
Ort / Verlag
Ireland: Elsevier B.V
Erscheinungsjahr
2018
Quelle
MEDLINE
Beschreibungen/Notizen
  • •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. 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.

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