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Journal of Neuroscience, Vol 16, 2444-2451, Copyright © 1996 by Society for Neuroscience
Protein synthesis-dependent formation of protein kinase Mzeta in long- term potentiation
P Osten, L Valsamis, A Harris and TC Sacktor
Department of Pharmacology, SUNY Health Science Center at Brooklyn, New York 11203, USA.
The maintenance of long-term potentiation (LTP) in the CA1 region of the
hippocampus has been reported to require both a persistent increase in
phosphorylation and the synthesis of new proteins. The increased activity
of protein kinase C (PKC) during the maintenance phase of LTP may result
from the formation of PKMzeta, the constitutively active fragment of a
specific PKC isozyme. To define the relationship among PKMzeta, long-term
EPSP responses, and the requirement for new protein synthesis, we examined
the regulation of PKMzeta after sub-threshold stimulation that produced
short-term potentiation (STP) and after suprathreshold stimulation by
single and multiple tetanic trains that produced LTP. We found that,
although no persistent increase in PKMzeta followed STP, the degree of
long-term EPSP potentiation was linearly correlated with the increase of
PKMzeta. The increase was first observed 10 min after a tetanus that
induced LTP and lasted for at least 2 hr, in parallel with the persistence
of EPSP enhancement. Both the maintenance of LTP and the long-term increase
in PKMzeta++ were blocked by the protein synthesis inhibitors anisomycin
and cycloheximide. These results suggest that PKMzeta is a component of a
protein synthesis-dependent mechanism for persistent phosphorylation in
LTP.
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