PKMζ, but not PKCλ, is rapidly synthesized and degraded at the neuronal synapse

Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correla...

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Published inThe Journal of neuroscience Vol. 35; no. 20; pp. 7736 - 7749
Main Authors Palida, Sakina F, Butko, Margaret T, Ngo, John T, Mackey, Mason R, Gross, Larry A, Ellisman, Mark H, Tsien, Roger Y
Format Journal Article
LanguageEnglish
Published United States Society for Neuroscience 20.05.2015
Subjects
Amino Acid Sequence
Animals
Cells, Cultured
Dendritic Spines - metabolism
Dendritic Spines - physiology
Enzyme Stability
HEK293 Cells
Humans
Isoenzymes - biosynthesis
Isoenzymes - genetics
Isoenzymes - metabolism
Long-Term Potentiation
Molecular Sequence Data
Protein Kinase C - genetics
Protein Kinase C - metabolism
Proteolysis
Rats
Rats, Sprague-Dawley
Synapses - metabolism
Synapses - physiology
Up-Regulation
protein kinases
protein synthesis
protein turnover
memory
synaptic plasticity
long-term potentiation
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Summary:Synthesizing, localizing, and stabilizing new protein copies at synapses are crucial factors in maintaining the synaptic changes required for storing long-term memories. PKMζ recently emerged as a molecule putatively responsible for maintaining encoded memories over time because its presence correlates with late LTP and because its inhibition disrupts LTP in vitro and long-term memory storage in vivo. Here we investigated PKMζ stability in rat neurons to better understand its role during information encoding and storage. We used TimeSTAMP reporters to track the synthesis and degradation of PKMζ as well as a related atypical PKC, PKCλ. These reporters revealed that both PKMζ and PKCλ were upregulated after chemical LTP induction; however, these new PKMζ copies exhibited more rapid turnover than basally produced PKMζ, particularly in dendritic spines. In contrast to PKMζ, new PKCλ copies exhibited elevated stability. Stable information storage over long periods of time is more challenging the shorter the metabolic lifetime of the candidate molecules.
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Author contributions: S.F.P., M.T.B., J.T.N., M.R.M., L.A.G., M.H.E., and R.Y.T. designed research; S.F.P., M.T.B., J.T.N., M.R.M., and L.A.G. performed research; S.F.P., M.T.B., J.T.N., M.R.M., L.A.G., M.H.E., and R.Y.T. analyzed data; S.F.P., M.H.E., and R.Y.T. wrote the paper.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0004-15.2015